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Introduction: The DAPA-CKD study showed a protective effect of dapagliflozin on kidney function in chronic kidney disease (CKD) patients with and without diabetes mellitus. Although dapagliflozin is expected to be effective also in CKD patients with autosomal dominant polycystic kidney disease (ADPKD), its efficacy and safety in this population remain unknown because ADPKD was an exclusion criterion in the DAPA-CKD study. Therefore, we evaluated the effects of dapagliflozin in CKD patients with ADPKD. Methods: We performed a retrospective observational study of seven patients with ADPKD treated with dapagliflozin at Toranomon Hospital, Tokyo, Japan. We analyzed changes in estimated glomerular filtration rate (eGFR) slope and annual height-corrected total kidney volume before and after starting dapagliflozin treatment. Results: The median observation period after starting dapagliflozin was 20 months. Four patients received concomitant tolvaptan. The eGFR slope before and after initiation of dapagliflozin could be calculated in six patients and improved in all of them except the one who did not receive a renin-angiotensin system (RAS) inhibitor. Annual height-corrected total kidney volume increased in all patients. Concurrent tolvaptan treatment had no effect. Conclusion: In CKD patients with ADPKD, dapagliflozin may increase kidney volume but may have a protective effect on kidney function when used concomitantly with RAS inhibitors.
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Background/aim: Total kidney volume (TKV) is a parameter used in both treatment decision and follow-up in autosomal dominant polycystic kidney disease (ADPKD) patients. The objective of this study was to evaluate intra- and interobserver agreement of the ellipsoid formula (EF) and manual boundary tracing method (MBTM) used in TKV measurement of ADPKD patients across different levels of experience radiologists. Additionally, the study aimed to evaluate the correlation between the EF and MBTM, which is considered the gold standard for TKV. Materials and methods: A retrospective evaluation was conducted on magnetic resonance imaging (MRI) data from 55 ADPKD patients who underwent abdominal MRI between January 2017 and November 2021 to evaluate TKV. TKV measurements were performed by three independent observers (observer 1, an abdominal imaging radiologist with 5 years of experience; observer 2, a fourth-year radiology resident; observer 3, a second-year radiology resident).To assess intraobserver variability, all observers repeated the measurements at two-week intervals. The ICC was used to assess both intraobserver and interobserver variability. A comparison of the two methods was performed by linear regression for all three observers. Results: The ICC (95% CI) indicated excellent agreement between the observers for both methods (among all observers, p < 0.001). Furthermore, excellent intraobserver agreement was found between all observer measurements either EF or MBTM based on ICC (95% CI) (p < 0.001). The results of the linear regression analysis demonstrated high correlations between the two methods in all three observers (r = 0.992, p < 0.001 for the first observer; r = 0.975, p < 0.001 for the second observer; r = 0.989, p < 0.001 for the third observer). Conclusion: Both the EF and MBTM methods used for the measurement of TKV provided excellent intra- and interobserver reproducibility. The EF is as accurate and precise as the MBTM. It may therefore be preferred in radiology departments with heavy workload, as it is a reliable method for rapid and easy assessment, independent of experience.
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Rim , Imageamento por Ressonância Magnética , Variações Dependentes do Observador , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Rim/diagnóstico por imagem , Rim/patologia , Adulto , Tamanho do Órgão , Reprodutibilidade dos TestesRESUMO
AIMS/HYPOTHESIS: The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV). METHODS: This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [ΔADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI. RESULTS: Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20×10-3 mm2/s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15×10-3 mm2/s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05×10-3 mm2/s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed ΔADC significantly from placebo, showing a decrease of -0.13×10-3 mm2/s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA1c. CONCLUSIONS/INTERPRETATION: In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38.
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BACKGROUND: Acute kidney injury (AKI) diagnosis often lacks a baseline serum creatinine (Cr) value. Our study aimed to create a regression equation linking kidney morphology to function in kidney donors and chronic kidney disease patients. We also sought to estimate baseline Cr in minimal change disease (MCD) patients, a common AKI-predisposing condition. METHODS: We analyzed 119 participants (mean age 60 years, 50% male, 40% donors) with CT scans, dividing them into derivation and validation groups. An equation based on kidney parenchymal volume (PV) was developed in the derivation group and validated in the validation group. We estimated baseline Cr in 43 MCD patients (mean age 45 years, 61% male) using the PV-based equation and compared with their 6 month post-MCD onset Cr values. RESULTS: In the derivation group, the equation for the estimated glomerular filtration rate (eGFR) was: eGFR (mL/min/1.73m2) = 0.375 × PV (cm3) + (- 0.395) × age (years) + (- 2.93) × male sex + (- 13.3) × hypertension + (- 14.0) × diabetes + (- 0.210) × height (cm) + 82.0 (intercept). In the validation group, the eGFR and estimated Cr values correlated well with the measured values (r = 0.46, p = 0.01; r = 0.51, p = 0.004, respectively). In the MCD group, the baseline Cr values were significantly correlated with the estimated baseline Cr values (r = 0.52, p < 0.001), effectively diagnosing AKI (kappa = 0.76, p < 0.001). CONCLUSIONS: The PV-based regression equation established in this study holds promise for estimating baseline Cr values and diagnosing AKI in patients with MCD. Further validation in diverse AKI populations is warranted.
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Introduction: The Mayo imaging classification model (MICM) requires a prestep qualitative assessment to determine whether a patient is in class 1 (typical) or class 2 (atypical), where patients assigned to class 2 are excluded from the MICM application. Methods: We developed a deep learning-based method to automatically classify class 1 and 2 from magnetic resonance (MR) images and provide classification confidence utilizing abdominal T 2 -weighted MR images from 486 subjects, where transfer learning was applied. In addition, the explainable artificial intelligence (XAI) method was illustrated to enhance the explainability of the automated classification results. For performance evaluations, confusion matrices were generated, and receiver operating characteristic curves were drawn to measure the area under the curve. Results: The proposed method showed excellent performance for the classification of class 1 (97.7%) and 2 (100%), where the combined test accuracy was 98.01%. The precision and recall for predicting class 1 were 1.00 and 0.98, respectively, with F 1 -score of 0.99; whereas those for predicting class 2 were 0.87 and 1.00, respectively, with F 1 -score of 0.93. The weighted averages of precision and recall were 0.98 and 0.98, respectively, showing the classification confidence scores whereas the XAI method well-highlighted contributing regions for the classification. Conclusion: The proposed automated method can classify class 1 and 2 cases as accurately as the level of a human expert. This method may be a useful tool to facilitate clinical trials investigating different types of kidney morphology and for clinical management of patients with autosomal dominant polycystic kidney disease (ADPKD).
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BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable. STUDY DESIGN: The National Institute of Child Health and Human Development Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (fifth, 50th, 95th percentiles) were derived from 15 to 41 weeks' using linear mixed models for repeated measures with cubic splines. RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid-arm and thigh circumferences were more linear. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic, or environmental influences and pregnancy complications, in ways not identifiable using corresponding 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.
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To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1-14 years old) and 12 adults (51-80 years old). Kidney volumes were measured from CT or MRI images during follow-up. Dose-volume histograms were calculated using a treatment planning system. In children, the median volume changes for the irradiated and control kidneys were -5.58 (-94.95 to +4.79) and +14.92 (-19.45 to +53.89) mL, respectively, with a relative volume change of -28.38 (-119.45 to -3.87) mL for the irradiated kidneys. For adults, these volume changes were -22.43 (-68.7 to -3.48) and -21.56 (-57.26 to -0.16) mL, respectively, with a relative volume change of -5.83 (-28.85 to +30.92) mL. Control kidneys in children exhibited a marked increase in size, while those in adults showed slight volumetric loss. The percentage of irradiated volume receiving 10 Gy (RBE) (V10) and 20 Gy (RBE) (V20) were significantly negatively associated with the relative volume change per year, especially in children. The CKD stage based on eGFR for all patients ranged from 1 to 3 and no cases with severe renal dysfunction were found before or after PBT. Late effects on the kidneys after PBT vary among age groups. Children are more susceptible than adults to significant renal atrophy after PBT. V10 and V20 might serve as predictors of the degree of renal atrophy after PBT, especially in children. PBT has a minimal impact on deterioration of renal function in both children and adults.
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BACKGROUND AND OBJECITVES: The currently available kidney volume normative values in children are restricted to small populations from single-centre studies not assessing kidney function and including none or only a small number of adolescents. This study aimed to obtain ultrasound-based kidney volume normative values derived from a large European White/Caucasian paediatric population with normal kidney function. METHODS: After recruitment of 1427 children aged 0-19 years, 1396 individuals with no history of kidney disease and normal estimated glomerular filtration rate were selected for the sonographic evaluation of kidney volume. Kidney volume was correlated with age, height, weight, body surface area and body mass index. Kidney volume curves and tables related to anthropometric parameters were generated using the LMS method. Kidney volume predictors were evaluated using multivariate regression analysis with collinearity checks. RESULTS: No clinically significant differences in kidney volume in relation to height were found between males and females, between supine and prone position and between left and right kidneys. Males had, however, larger age-related kidney volumes than females in most age categories. For the prediction of kidney volume, the highest coefficient correlation was observed for body surface area (r = 0.94), followed by weight (r = 0.92), height (r = 0.91), age (r = 0.91), and body mass index (r = 0.67; p < 0.001 for all). CONCLUSIONS: This study presents LMS-percentile curves and tables for kidney volume which can be used as reference values for children aged 0-19 years.
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Rim , Ultrassonografia , Humanos , Adolescente , Criança , Masculino , Feminino , Lactente , Pré-Escolar , Rim/diagnóstico por imagem , Rim/anatomia & histologia , Valores de Referência , Tamanho do Órgão , Recém-Nascido , Adulto Jovem , Índice de Massa Corporal , Taxa de Filtração Glomerular , Fatores Etários , Europa (Continente) , Peso CorporalRESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney disease (ESKD) worldwide. Guidelines for the diagnosis and management of ADPKD in Taiwan remains unavailable. In this consensus statement, we summarize updated information on clinical features of international and domestic patients with ADPKD, followed by suggestions for optimal diagnosis and care in Taiwan. Specifically, counselling for at-risk minors and reproductive issues can be important, including ethical dilemmas surrounding prenatal diagnosis and pre-implantation genetic diagnosis. Studies reveal that ADPKD typically remains asymptomatic until the fourth decade of life, with symptoms resulting from cystic expansion with visceral compression, or rupture. The diagnosis can be made based on a detailed family history, followed by imaging studies (ultrasound, computed tomography, or magnetic resonance imaging). Genetic testing is reserved for atypical cases mostly. Common tools for prognosis prediction include total kidney volume, Mayo classification and PROPKD/genetic score. Screening and management of complications such as hypertension, proteinuria, urological infections, intracranial aneurysms, are also crucial for improving outcome. We suggest that the optimal management strategies of patients with ADPKD include general medical care, dietary recommendations and ADPKD-specific treatments. Key points include rigorous blood pressure control, dietary sodium restriction and Tolvaptan use, whereas the evidence for somatostatin analogues and mammalian target of rapamycin (mTOR) inhibitors remains limited. In summary, we outline an individualized care plan emphasizing careful monitoring of disease progression and highlight the need for shared decision-making among these patients.
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Falência Renal Crônica , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/terapia , Rim Policístico Autossômico Dominante/complicações , Taiwan/epidemiologia , Tolvaptan , RimRESUMO
Introduction: In the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups. Methods: This multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5-18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV. Results: Median (Q1-Q3) age of the patients was 6.0 (2.0-10.0) years, 56% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89% had PKD1 and 11% had PKD2 mutations. Non-missense mutations were 73% in PKD1 and 75% in PKD2. Twenty patients (27%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117â ml/m, p = 0.0003). LIC stratification revealed Classes A (38.7%), B (28%), C (24%), and D + E (9.3%). All children in class D + E and 94% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes (p > 0.05 for all). Discussion: This study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies.
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BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder that causes uncontrolled kidney cyst growth, leading to kidney volume enlargement and renal function loss over time. Total kidney volume (TKV) and cyst burdens have been used as prognostic imaging biomarkers for ADPKD. OBJECTIVE: This study aimed to evaluate nnUNet for automatic kidney and cyst segmentation in T2-weighted (T2W) MRI images of ADPKD patients. METHODS: 756 kidney images were retrieved from 95 patients in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort (95 patients × 2 kidneys × 4 follow-up scans). The nnUNet model was trained, validated, and tested on 604, 76, and 76 images, respectively. In contrast, all images of each patient were exclusively assigned to either the training, validation, or test sets to minimize evaluation bias. The kidney and cyst regions defined using a semi-automatic method were employed as ground truth. The model performance was assessed using the Dice Similarity Coefficient (DSC), the intersection over union (IoU) score, and the Hausdorff distance (HD). RESULTS: The test DSC values were 0.96±0.01 (mean±SD) and 0.90±0.05 for kidney and cysts, respectively. Similarly, the IoU scores were 0.91± 0.09 and 0.81±0.06, and the HD values were 12.49±8.71 mm and 12.04±10.41 mm, respectively, for kidney and cyst segmentation. CONCLUSION: The nnUNet model is a reliable tool to automatically determine kidney and cyst volumes in T2W MRI images for ADPKD prognosis and therapy monitoring.
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Cistos , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Rim/diagnóstico por imagemRESUMO
Introduction: Accurate tools to inform individual prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD) are lacking. Here, we report an artificial intelligence (AI)-generated method for routinely measuring total kidney volume (TKV). Methods: An ensemble U-net algorithm was created using the nnUNet approach. The training and internal cross-validation cohort consisted of all 1.5T magnetic resonance imaging (MRI) data acquired using 5 different MRI scanners (454 kidneys, 227 scans) in the CYSTic consortium, which was first manually segmented by a single human operator. As an independent validation cohort, we utilized 48 sequential clinical MRI scans with reference results of manual segmentation acquired by 6 individual analysts at a single center. The tool was then implemented for clinical use and its performance analyzed. Results: The training or internal validation cohort was younger (mean age 44.0 vs. 51.5 years) and the female-to-male ratio higher (1.2 vs. 0.94) compared to the clinical validation cohort. The majority of CYSTic patients had PKD1 mutations (79%) and typical disease (Mayo Imaging class 1, 86%). The median DICE score on the clinical validation data set between the algorithm and human analysts was 0.96 for left and right kidneys with a median TKV error of -1.8%. The time taken to manually segment kidneys in the CYSTic data set was 56 (±28) minutes, whereas manual corrections of the algorithm output took 8.5 (±9.2) minutes per scan. Conclusion: Our AI-based algorithm demonstrates performance comparable to manual segmentation. Its rapidity and precision in real-world clinical cases demonstrate its suitability for clinical application.
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INTRODUCTION: Our main objective was to identify baseline prognostic factors predictive of rapid disease progression in a large unselected clinical autosomal dominant polycystic kidney disease (ADPKD) cohort. METHODS: A cross-sectional analysis was performed in 618 consecutive ADPKD patients assessed and followed-up for over a decade. A total of 123 patients (19.9%) had reached kidney failure by the study date. Data were available for the following: baseline eGFR (n = 501), genotype (n = 549), baseline ultrasound mean kidney length (MKL, n = 424) and height-adjusted baseline MKL (HtMKL, n = 377). Rapid disease progression was defined as an annualized eGFR decline (∆eGFR) of >2.5 mL/min/year by linear regression over 5 years (n = 158). Patients were further divided into slow, rapid and very rapid ∆eGFR classes for analysis. Genotyped patients were classified into several categories: PKD1 (T, truncating; or NT, non-truncating), PKD2, other genes (non-PKD1 or -PKD2), no mutation detected or variants of uncertain significance. RESULTS: A PKD1-T genotype had the strongest influence on the probability of reduced baseline kidney function by age. A multivariate logistic regression model identified PKD1-T genotype and HtMKL (>9.5 cm/m) as independent predictors for rapid disease progression. The combination of both factors increased the positive predictive value for rapid disease progression over age 40 years and of reaching kidney failure by age 60 years to 100%. Exploratory analysis in a subgroup with available total kidney volumes showed higher positive predictive value (100% vs 80%) and negative predictive value (42% vs 33%) in predicting rapid disease progression compared with the Mayo Imaging Classification (1C-E). CONCLUSION: Real-world longitudinal data confirm the importance of genotype and kidney length as independent variables determining ∆eGFR. Individuals with the highest risk of rapid disease progression can be positively selected for treatment based on this combination.
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Progressão da Doença , Genótipo , Taxa de Filtração Glomerular , Rim , Rim Policístico Autossômico Dominante , Canais de Cátion TRPP , Humanos , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/patologia , Masculino , Feminino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Rim/patologia , Rim/diagnóstico por imagem , Prognóstico , Seguimentos , Canais de Cátion TRPP/genética , Estatura/genéticaRESUMO
BACKGROUND: Selecting the smaller kidney for donation has been advocated if there is a size difference of > 10% between the 2 kidneys but has never been prospectively evaluated. With increase in donor nephrectomies, it is important to evaluate this to minimize loss of renal function to donors. METHODS: 75 consecutive donor nephrectomy patients were included in our longitudinal study. The Split Renal Volume (SRV) of bilateral kidneys were measured using contrasted computer tomography scans and patients segregated into 2 groups depending on donated kidney having more (Group 1) or less than (Group 2) 52.5% of SRV. RESULTS: Patients in Group 1 (n = 19) and 2 (n = 56) were of similar age (43.8 vs. 48.3), BMI (22.4 vs. 25.2), sex (57.9 vs. 55.4% women), respectively. Although total kidney volumes were similar in both groups, Group 1 had significantly smaller right kidney volumes (120.4 ± 24.9 vs. 142.7 ± 28.4 mls, p = 0.003). EGFR pre-operatively (116.3 ± 20.8 vs. 106.3 ± 23.8 mL/min/1.73 m2) and at 6-months (65.7 ± 13.3 vs. 66.9 ± 15.5 mL/min/1.73 m2) were not different between groups. However, patients in Group 1 had significantly greater absolute (50.6 ± 14.9 vs. 39.5 ± 14.7 mL/min/1.73 m2) and relative decline (43.0 ± 8.6 vs. 36.3 ± 10.6%) in eGFR at 6 months (p = 0.06, 0.009). CONCLUSION: With a SRV difference of 5% between the 2 sides, removal of the larger kidney for living kidney donation resulted in greater early decline of renal function than kidney donors whose larger or equivalent kidney is preserved.
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Transplante de Rim , Humanos , Feminino , Masculino , Transplante de Rim/métodos , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Doadores Vivos , Estudos Longitudinais , Estudos Retrospectivos , Rim/diagnóstico por imagem , Taxa de Filtração Glomerular , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Tolvaptan preserves kidney function in adults with autosomal dominant polycystic kidney disease (ADPKD) at elevated risk of rapid progression. A trial (NCT02964273) evaluated tolvaptan safety and pharmacodynamics in children (5-17 years). However, progression risk was not part of study eligibility criteria due to lack of validated criteria for risk assessment in children. As risk estimation is important to guide clinical management, baseline characteristics of the study participants were retrospectively evaluated to determine whether risk of rapid disease progression in pediatric ADPKD can be assessed and to identify parameters relevant for risk estimation. METHODS: Four academic pediatric nephrologists reviewed baseline data and rated participant risk from 1 (lowest) to 5 (highest) based on clinical judgement and the literature. Three primary reviewers independently scored all cases, with each case reviewed by two primary reviewers. For cases with discordant ratings (≥ 2-point difference), the fourth reviewer provided a secondary rating blinded to the primary evaluations. Study participants with discordant ratings and/or for whom data were lacking were later discussed to clarify parameters relevant to risk estimation. RESULTS: Of 90 evaluable subjects, primary reviews of 69 (77%) were concordant. The proportion considered at risk of rapid progression (final mean rating ≥ 3.5) by age group was: 15-17 years, 27/34 (79%); 12- < 15, 9/32 (28%); 4- < 12, 8/24 (33%). The panelists agreed on characteristics important for risk determination: age, kidney imaging, kidney function, blood pressure, urine protein, and genetics. CONCLUSIONS: High ratings concordance and agreement among reviewers on relevant clinical characteristics support the feasibility of pediatric risk assessment.
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Rim Policístico Autossômico Dominante , Tolvaptan , Adolescente , Criança , Humanos , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Progressão da Doença , Taxa de Filtração Glomerular , Rim , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/tratamento farmacológico , Estudos Retrospectivos , Tolvaptan/efeitos adversosRESUMO
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and continued growth of multiple cysts in the kidneys leading to ultimate loss of kidney function in most patients. Currently, tolvaptan is the only agency approved therapy to slow kidney disease advancement in patients with faster progressing disease underscoring the need for additional ADPKD therapies suitable for all patients. We previously showed that pravastatin slowed kidney disease progression in children and young adults with ADPKD. However, the intervention has not been tested in an adult cohort. AIMS: The aim of the study is to conduct a single center, randomized, placebo-controlled double-blinded clinical trial to determine the efficacy of pravastatin on slowing kidney disease progression in adult patients with early stage ADPKD. METHODS: One hundred and fifty adult patients with ADPKD and eGFR ≥60 ml/min/1.73m2 will be enrolled in the study and randomized to receive 40 mg/day pravastatin or placebo for a period of 2-years. OUTCOMES: The primary outcome of the trial is change in total kidney volume assessed by magnetic resonance imaging (MRI). Secondary outcomes include change in kidney function by iothalamate GFR and renal blood flow and markers of inflammation and oxidative stress. CONCLUSION: This study will assess the kidney therapeutic benefits of pravastatin in adult patients with ADPKD. The recruitment goal of 150 subjects was attained and the study is ongoing. REGISTRATION: This study is registered on Clinicaltrials.gov # NCT03273413.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Rim Policístico Autossômico Dominante , Adulto Jovem , Criança , Humanos , Adulto , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pravastatina/uso terapêutico , Método Duplo-Cego , Progressão da Doença , Taxa de Filtração GlomerularRESUMO
To date, there is insufficient evidence regarding use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with autosomal-dominant polycystic kidney disease (ADPKD), as such cases have been excluded from previous clinical trials exploring the kidney protection effects of such medications. Here, findings of an ADPKD patient who received dapagliflozin, a selective SGLT2 inhibitor, for 1 year are presented. A 38-year-old woman with a family history of ADPKD wished for treatment with dapagliflozin. After starting administration at 10 mg/day, total kidney volume (TKV) continued to increase, from 1641 to 1764 mL after 84 days and then to 2297 mL after 340 days. The estimated glomerular filtration rate (eGFR) was also decreased from 67.3 to 56.2 mL/min/1.73 m2, and then to 51.4 mL/min/1.73 m2 at those times. Immediately after discontinuation of dapagliflozin, TKV and eGFR were slightly improved to 2263 mL and 55.1 mL/min/1.73 m2, respectively. Following a review of basic research studies, we consider that increased intratubular urinary osmotic pressure, compensatory glucose reabsorption by sodium-glucose cotransporter-1 in the late proximal tubule, and hypertrophy shown in collected cells caused by increased vasopressin may be associated with ADPKD disease progression. Caution may be needed when administering dapagliflozin to patients with ADPKD.
Assuntos
Compostos Benzidrílicos , Taxa de Filtração Glomerular , Glucosídeos , Rim , Rim Policístico Autossômico Dominante , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/complicações , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/administração & dosagem , Feminino , Adulto , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Rim/patologia , Taxa de Filtração Glomerular/efeitos dos fármacosRESUMO
Background: Renal disease is a major problem in terms of community health and the economy. Skeletal muscle is involved in crosstalk with the kidney. We therefore investigated the relationship between muscle quality and quantity, and renal parenchymal volume (RPV). Methods: The association between the parameters of skeletal muscle and RPV/body surface area (BSA) was analyzed by computed tomography in 728 middle-aged participants without kidney disease or diabetes mellitus in a cross-sectional study. A retrospective cohort study of 68 participants was undertaken to analyze the association between changes in RPV/BSA and muscle parameters. Parameter change was calculated as follows: parameter at the follow-up examination/parameter at the baseline examination. The normal attenuation muscle (NAM) and low attenuation muscle (LAM) were identified by Hounsfield Unit thresholds of +30 to +150, and -29 to +29, respectively. Results: Positive correlations were found between estimated glomerular filtration rate and RPV/BSA (r = 0.451, P < .0001). Multiple regression analyses revealed that the NAM index was positively related to RPV/BSA (ß = 0.458, P < .0001), whereas the LAM index was negatively related to RPV/BSA (ß = -0.237, P < .0001). In this cohort study, a change in the LAM index was independently associated with a change in RPV/BSA (ß = -0.349, P = .0032). Conclusion: Both trunk muscle quantity and quality were associated with renal volume related to renal function in nondiabetic people. An increase in low quality muscle volume might be related to a decrease in renal volume.
RESUMO
BACKGROUND: Organ measurements derived from magnetic resonance imaging (MRI) have the potential to enhance our understanding of the precise phenotypic variations underlying many clinical conditions. METHODS: We applied morphometric methods to study the kidneys by constructing surface meshes from kidney segmentations from abdominal MRI data in 38,868 participants in the UK Biobank. Using mesh-based analysis techniques based on statistical parametric maps (SPMs), we were able to detect variations in specific regions of the kidney and associate those with anthropometric traits as well as disease states including chronic kidney disease (CKD), type-2 diabetes (T2D), and hypertension. Statistical shape analysis (SSA) based on principal component analysis was also used within the disease population and the principal component scores were used to assess the risk of disease events. RESULTS: We show that CKD, T2D and hypertension were associated with kidney shape. Age was associated with kidney shape consistently across disease groups. Body mass index (BMI) and waist-to-hip ratio (WHR) were also associated with kidney shape for the participants with T2D. Using SSA, we were able to capture kidney shape variations, relative to size, angle, straightness, width, length, and thickness of the kidneys, within disease populations. We identified significant associations between both left and right kidney length and width and incidence of CKD (hazard ratio (HR): 0.74, 95% CI: 0.61-0.90, p < 0.05, in the left kidney; HR: 0.76, 95% CI: 0.63-0.92, p < 0.05, in the right kidney) and hypertension (HR: 1.16, 95% CI: 1.03-1.29, p < 0.05, in the left kidney; HR: 0.87, 95% CI: 0.79-0.96, p < 0.05, in the right kidney). CONCLUSIONS: The results suggest that shape-based analysis of the kidneys can augment studies aiming at the better categorisation of pathologies associated with chronic kidney conditions.
Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Insuficiência Renal Crônica , Humanos , Rim/diagnóstico por imagem , Antropometria , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/epidemiologia , Índice de Massa Corporal , Hipertensão/diagnóstico por imagem , Hipertensão/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de RiscoRESUMO
Background: For decades, description of renal function has been of interest to clinicians and researchers. Serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) are familiar but also limited in many circumstances. Meanwhile, the physiological volumes of the kidney cortex and medulla are presumed to change with age and have been proven to change with decreasing kidney function. Methods: We recruited 182 patients with normal Scr levels between October 2021 and February 2022 in Peking Union Medical College Hospital (PUMCH) with demographic and clinical data. A 3D U-Net architecture is used for both cortex and medullary separation, and volume calculation. In addition, we included patients with the same inclusion criteria but with diabetes (PUMCH-DM test set) and diabetic nephropathy (PUMCH-DN test set) for internal comparison to verify the possible clinical value of "kidney age" (K-AGE). Results: The PUMCH training set included 146 participants with a mean age of 47.5 ± 7.4 years and mean Scr 63.5 ± 12.3 µmol/L. The PUMCH test set included 36 participants with a mean age of 47.1 ± 7.9 years and mean Scr 66.9 ± 13.0 µmol/L. The multimodal method predicted K-AGE approximately close to the patient's actual physiological age, with 92% prediction within the 95% confidential interval. The mean absolute error increases with disease progression (PUMCH 5.00, PUMCH-DM 6.99, PUMCH-DN 9.32). Conclusion: We established a machine learning model for predicting the K-AGE, which offered the possibility of evaluating the whole kidney health in normal kidney aging and in disease conditions.