Search

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. [ABSTRACT FROM AUTHOR]

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. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding the age-specific effects of proton beam therapy (PBT) on kidney function is crucial for personalized treatment. This study compared the long-term impact of PBT on kidneys in pediatric and adult patients with adjacent malignancies. Findings reveal that children are more prone to renal atrophy post-PBT compared to adults, who experience minimal changes in kidney morphology. The percentage of irradiated volume receiving 10 Gy (RBE) and 20 Gy (RBE) may predict the degree of renal atrophy, especially in children. PBT has minimal impact on renal function deterioration in both age groups. This research informs treatment plans for patients in different ages, aiming to minimize renal complications and provide insights for personalized cancer care, ensuring better long-term kidney health outcomes and overall quality of life. 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. [ABSTRACT FROM AUTHOR]

Renal ultrasound is a convenient, safe, and affordable tool for visualization of the kidneys in the daily practice of nephrologists and doctors of other specialties. Kidney volume, which is calculated by the sonographic method, gives an idea about the state of the kidneys of the patient, but says almost nothing about their function. There are many studies of renal index of resistance (IR) as a marker of kidney function. IR values were compared with serum creatinine levels and/or histological data. And although conflicting research data limit the use of IR as a marker of kidney function, correct interpretation of IR helps restore it to the status of a candidate marker of kidney function. The purpose of the study: to conduct a retrospective analysis of the sonographic renal parameters in patients who sought outpatient medical care at the Brovary medical institution. Materials and methods. Retrospective randomized cohort study was conducted of sonograms of 66 outpatients who sought outpatient medical care at a private medical facility in Brovary from February 2022 to February 2024. They were divided into 2 groups: the first one (n = 31) — men and the second group (n = 35) — women. Results. The results of multiple linear regression in the group 1 for right kidney (RK) showed that the independent variable in this model, RK thickness, is of low significance as a predictor for IR RK, and the following independent variables were not significant as predictors for IR RK: RK length, RK width, RK volume, age. Multiple linear regression results in the group 1 for left kidney (LK) indicate that the independent variable in this model, LK width, is moderately significant as a predictor for LK IR, and the following independent variables were not significant as predictors for LK IR: LK length, LK thickness, LK volume, age. Multiple linear regression results in the group 2 for RK showed that the independent variables in this model, RK width and age, are significant as predictors for IR RK, and the following independent variables were not significant as predictors for IR RK: RK length, RK thickness, RK volume. Multiple linear regression results in the group 2 for LK indicate that the independent variable in this model, LK width, is moderately significant as a predictor for LK IR, and the following independent variables were not significant as predictors for LK IR: LK length, LK thickness, LK volume, age. Conclusions. Renal ultrasound allows predicting the category of patients who will need a consultation with a nephrologist/urologist, identifying risk groups for chronic kidney disease. [ABSTRACT FROM AUTHOR]

Abstract 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

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. [ABSTRACT FROM AUTHOR]

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 (β = 0.458, P  < .0001), whereas the LAM index was negatively related to RPV/BSA (β = –0.237, P  < .0001). In this cohort study, a change in the LAM index was independently associated with a change in RPV/BSA (β = –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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Total kidney volume (TKV) is an important biomarker for assessing kidney function, especially for autosomal dominant polycystic kidney disease (ADPKD). However, TKV measurements from a single MRI pulse sequence have limited reproducibility, ± ~5%, similar to ADPKD annual kidney growth rates. Purpose: To improve TKV measurement reproducibility on MRI by extending artificial intelligence algorithms to automatically segment kidneys on T1‐weighted, T2‐weighted, and steady state free precession (SSFP) sequences in axial and coronal planes and averaging measurements. Study Type: Retrospective training, prospective testing. Subjects: Three hundred ninety‐seven patients (356 with ADPKD, 41 without), 75% for training and 25% for validation, 40 ADPKD patients for testing and 17 ADPKD patients for assessing reproducibility. Field Strength/Sequence: T2‐weighted single‐shot fast spin echo (T2), SSFP, and T1‐weighted 3D spoiled gradient echo (T1) at 1.5 and 3T. Assessment: 2D U‐net segmentation algorithm was trained on images from all sequences. Five observers independently measured each kidney volume manually on axial T2 and using model‐assisted segmentations on all sequences and image plane orientations for two MRI exams in two sessions separated by 1–3 weeks to assess reproducibility. Manual and model‐assisted segmentation times were recorded. Statistical Tests: Bland–Altman, Schapiro–Wilk (normality assessment), Pearson's chi‐squared (categorical variables); Dice similarity coefficient, interclass correlation coefficient, and concordance correlation coefficient for analyzing TKV reproducibility. P‐value < 0.05 was considered statistically significant. Results: In 17 ADPKD subjects, model‐assisted segmentations of axial T2 images were significantly faster than manual segmentations (2:49 minute vs. 11:34 minute), with no significant absolute percent difference in TKV (5.9% vs. 5.3%, P = 0.88) between scans 1 and 2. Absolute percent differences between the two scans for model‐assisted segmentations on other sequences were 5.5% (axial T1), 4.5% (axial SSFP), 4.1% (coronal SSFP), and 3.2% (coronal T2). Averaging measurements from all five model‐assisted segmentations significantly reduced absolute percent difference to 2.5%, further improving to 2.1% after excluding an outlier. Data Conclusion: Measuring TKV on multiple MRI pulse sequences in coronal and axial planes is practical with deep learning model‐assisted segmentations and can improve TKV measurement reproducibility more than 2‐fold in ADPKD. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

IntroductionIn 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.MethodsThis 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.ResultsMedian (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. 117 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).DiscussionThis 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.

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.

Abstract Background Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) who are at risk of rapid progression. Given that treatment requires commitment to long-term use, we evaluated the effects of tolvaptan discontinuation on the trajectory of ADPKD progression. Methods This was a post hoc analysis of pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]) that enrolled patients from the other trials. Individual subject data were linked longitudinally across trials to construct analysis cohorts of subjects with a tolvaptan treatment duration > 180 days followed by an off-treatment observation period of > 180 days. For inclusion in Cohort 1, subjects were required have ≥ 2 outcome assessments during the tolvaptan treatment period and ≥ 2 assessments during the follow-up period. For Cohort 2, subjects were required to have ≥ 1 assessment during the tolvaptan treatment period and ≥ 1 assessment during the follow-up period. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). Piecewise-mixed models compared changes in eGFR or TKV in the on-treatment and post-treatment periods. Results In the Cohort 1 eGFR population (n = 20), the annual rate of eGFR change (in mL/min/1.73 m2) was -3.18 on treatment and -4.33 post-treatment, a difference that was not significant (P = 0.16), whereas in Cohort 2 (n = 82), the difference between on treatment (-1.89) and post-treatment (-4.94) was significant (P

Introduction: Renal functional response (RFR) is the acute increase in glomerular filtration rate (GFR) after a protein load. Low RFR is a marker of single nephron hyperfiltration. Low birth weight (LBW) is associated with reduced number of nephrons, lower kidney function, and smaller kidneys in adults. In the present study, we investigate the associations among LBW, kidney volume, and RFR. Methods: We studied adults aged 41 to 52 years born with either LBW (≤2300 g) or normal birth weight (NBW; 3500–4000 g). GFR was measured using plasma clearance of iohexol. A stimulated GFR (sGFR) was measured on a separate day after a protein load of 100 g using a commercially available protein powder, and RFR was calculated as delta GFR. Kidney volume was estimated from magnetic resonance imaging (MRI) images using the ellipsoid formula. Results: A total of 57 women and 48 men participated. The baseline mean ± SD GFR was 118 ± 17 ml/min for men and 98 ± 19 ml/min for women. The overall mean RFR was 8.2 ± 7.4 ml/min, with mean RFR of 8.3 ± 8.0 ml/min and 8.1 ± 6.9 ml/min in men and women, respectively (P = 0.5). No birth-related variables were associated with RFR. Larger kidney volume was associated with higher RFR, 1.9 ml/min per SD higher kidney volume (P = 0.009). Higher GFR per kidney volume was associated with a lower RFR, −3.3ml/min per SD (P < 0.001). Conclusion: Larger kidney size and lower GFR per kidney volume were associated with higher RFR. Birth weight was not shown to associate with RFR in mainly healthy middle-aged men and women.

Background: Accurate estimation of kidney size and volume in the solitary functioning kidney is crucial because of a higher risk of developing kidney injury. MRI is an accurate method and is suitable for kidney volume measurement. Usually, axial axis images and measurement methods are preferred for kidney volume measurements. However, the anteroposterior diameter of the kidney is smaller than the longitudinal diameter, meaning that imaging in the coronal axis could provide needed information in a shorter time, enabling imaging of younger patients without sedation. Therefore, the purpose of this study was to compare coronal and axial axis kidney volume measurement methods and evaluate intra-observer and inter-observer reliability. Methods: Axial axis T2W and coronal axis FIESTA images of kidneys were obtained with 10 mm slice thickness and no slice gap in pediatric patients with congenital solitary kidneys. Free-hand manual tracing was used to calculate volumes in both methods. Images were analyzed by two operators with different levels of experience. The expert operator computed solitary kidney volume twice in both methods for the intra-observer reliability, while the beginner operator's measurements were used for the inter-observer reliability. Results: High intra-observer (0.965 for axial and 0.972 for coronal) and inter-observer reliability were revealed (0.964 for axial and 0.963 for the coronal) for both measurement methods. Conclusion: The coronal plane volume measurement method, which has a significantly shorter examination and post-processing time, is a highly reproducible and reliable method that can enable volume measurement with MRI in younger children, as the imaging time will be shortened. [ABSTRACT FROM AUTHOR]

Abstract Background Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7–11 years. Methods Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm3) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7–11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders. Results Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure. Conclusion Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required.

Background: Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) who are at risk of rapid progression. Given that treatment requires commitment to long-term use, we evaluated the effects of tolvaptan discontinuation on the trajectory of ADPKD progression. Methods: This was a post hoc analysis of pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]) that enrolled patients from the other trials. Individual subject data were linked longitudinally across trials to construct analysis cohorts of subjects with a tolvaptan treatment duration > 180 days followed by an off-treatment observation period of > 180 days. For inclusion in Cohort 1, subjects were required have ≥ 2 outcome assessments during the tolvaptan treatment period and ≥ 2 assessments during the follow-up period. For Cohort 2, subjects were required to have ≥ 1 assessment during the tolvaptan treatment period and ≥ 1 assessment during the follow-up period. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). Piecewise-mixed models compared changes in eGFR or TKV in the on-treatment and post-treatment periods. Results: In the Cohort 1 eGFR population (n = 20), the annual rate of eGFR change (in mL/min/1.73 m2) was -3.18 on treatment and -4.33 post-treatment, a difference that was not significant (P = 0.16), whereas in Cohort 2 (n = 82), the difference between on treatment (-1.89) and post-treatment (-4.94) was significant (P < 0.001). In the Cohort 1 TKV population (n = 11), TKV increased annually by 5.18% on treatment and 11.69% post-treatment (P = 0.06). In Cohort 2 (n = 88), the annual TKV growth rates were 5.15% on treatment and 8.16% post-treatment (P = 0.001). Conclusions: Although limited by small sample sizes, these analyses showed directionally consistent acceleration in measures of ADPKD progression following the discontinuation of tolvaptan. [ABSTRACT FROM AUTHOR]

Background: Preterm birth and fetal growth restriction (FGR) are associated with structural and functional kidney changes, increasing long-term risk for chronic kidney disease and hypertension. However, recent studies in preterm children are conflicting, indicating structural changes but normal kidney function. This study therefore assessed kidney structure and function in a cohort of adolescents born very preterm with and without verified FGR. Methods: Adolescents born very preterm with FGR and two groups with appropriate birthweight (AGA) were included; one matched for gestational week at birth and one born at term. Cortical and medullary kidney volumes and T1 and T2* mapping values were assessed by magnetic resonance imaging. Biochemical markers of kidney function and renin–angiotensin–aldosterone system (RAAS) activation were analyzed. Results: Sixty-four adolescents were included (13–16 years; 48% girls). Very preterm birth with FGR showed smaller total (66 vs. 75 ml/m2; p = 0.01) and medullary volume (19 vs. 24 ml/m2; p < 0.0001) compared to term AGA. Corticomedullary volume ratio decreased from preterm FGR (2.4) to preterm AGA (2.2) to term AGA (1.9; p = 0.004). There were no differences in T1 or T2* values (all p ≥ 0.34) or in biochemical markers (all p ≥ 0.12) between groups. Conclusions: FGR with abnormal fetal blood flow followed by very preterm birth is associated with smaller total kidney and medullary kidney volumes, but not with markers of kidney dysfunction or RAAS activation in adolescence. Decreased total kidney and medullary volumes may still precede a long-term decrease in kidney function, and potentially be used as a prognostic marker. [ABSTRACT FROM AUTHOR]

Organ volume measurements are a key metric for managing ADPKD (the most common inherited renal disease). However, measuring organ volumes is tedious and involves manually contouring organ outlines on multiple cross-sectional MRI or CT images. The automation of kidney contouring using deep learning has been proposed, as it has small errors compared to manual contouring. Here, a deployed open-source deep learning ADPKD kidney segmentation pipeline is extended to also measure liver and spleen volumes, which are also important. This 2D U-net deep learning approach was developed with radiologist labeled T2-weighted images from 215 ADPKD subjects (70% training = 151, 30% validation = 64). Additional ADPKD subjects were utilized for prospective (n = 30) and external (n = 30) validations for a total of 275 subjects. Image cropping previously optimized for kidneys was included in training but removed for the validation and inference to accommodate the liver which is closer to the image border. An effective algorithm was developed to adjudicate overlap voxels that are labeled as more than one organ. Left kidney, right kidney, liver and spleen labels had average errors of 3%, 7%, 3%, and 1%, respectively, on external validation and 5%, 6%, 5%, and 1% on prospective validation. Dice scores also showed that the deep learning model was close to the radiologist contouring, measuring 0.98, 0.96, 0.97 and 0.96 on external validation and 0.96, 0.96, 0.96 and 0.95 on prospective validation for left kidney, right kidney, liver and spleen, respectively. The time required for manual correction of deep learning segmentation errors was only 19:17 min compared to 33:04 min for manual segmentations, a 42% time saving (p = 0.004). Standard deviation of model assisted segmentations was reduced to 7, 5, 11, 5 mL for right kidney, left kidney, liver and spleen respectively from 14, 10, 55 and 14 mL for manual segmentations. Thus, deep learning reduces the radiologist time required to perform multiorgan segmentations in ADPKD and reduces measurement variability.

Background: Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7–11 years. Methods: Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm3) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7–11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders. Results: Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure. Conclusion: Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required. [ABSTRACT FROM AUTHOR]

Aims: Whether different diabetic kidney disease (DKD) phenotypes recognise differences in morphological and vascular properties of the kidney is still unexplored. We evaluated the potential role of kidney ultrasonography in differentiating DKD phenotypes in subjects with type 2 diabetes. Materials and Methods: This is a cross‐sectional, single‐centre study. Total (TRV) and parenchymal renal volumes (PRV) were calculated by applying the ellipsoid formula for conventional (2D) ultrasonography and with manual segmentation for 3D ultrasonography, and then adjusted for body surface area (aTRV, aPRV). Renal resistive index (RI) was contextually determined. DKD phenotypes have been defined based on increased urinary albumin‐to‐creatinine ratio (ACR >30 mg/g) and/or reduced eGFR (<60 ml/min/1.73 m2). Recruitment was planned to have groups of the same size. Results: Among 256 subjects, 26.2% had No‐DKD, 24.6% increased albuminuria only (Alb+), 24.2% non‐albuminuric DKD (Alb−DKD), and 25.0% albuminuric DKD (Alb+DKD). Compared to No‐DKD, RI was significantly higher in all DKD phenotypes, being the highest in Alb+DKD, and with a significant trend of RI > 0.70 to increase across phenotypes. In comparison with No‐DKD, both 2D and 3D volumes were increased in Alb+ and significantly reduced in Alb−DKD as well as in Alb+DKD, with significantly lower volumes in Alb−DKD as compared to Alb+DKD at the same reduced levels of eGFR. In adjusted regressions, compared to No‐DKD, RI was associated with Alb+; both RI and aPRV3D were associated with Alb+DKD; only aPRV3D with Alb‐DKD. Compared to No‐DKD, Receiver Operating Characteristic curve analyses, designed taking into account conventional risk factors, showed that US parameters did not ameliorate the characterisation of Alb+ and Alb+DKD, while aPRV3D significantly improved the phenotyping of Alb‐DKD. Conclusions: As a novel information, we reported that, in type 2 diabetes, the emerging normoalbuminuric DKD phenotype showed reduced TRVs and PRVs even when compared, at similarly reduced eGFR levels, with Alb+DKD opening. In perspective, these findings suggest a possible role of imaging for better discrimination of DKD phenotypes in clinical practice. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Kidney transplant is a mainstay of kidney replacement therapy. Given a continued shortage of organs, pediatric en bloc kidney transplants may have substantial utility. We present our long-term experience with en bloc transplants from donors aged 3 to 60 months, including changes in kidney function and kidney volume over time as well as biopsy findings. Study Design: Case series. Setting & Participants: Medical records from a single academic medical center were reviewed. Aggregate serial volumes of 22 en bloc kidney allografts from 2010 to 2017 were assessed at the time of transplant and during follow-up. Estimated glomerular filtration rates (eGFR) were described at 3 months after transplant (baseline) as well as over the ensuing 3 years. Interstitial fibrosis, a finding determined by histopathologic review, which results from an accumulation of collagen that is produced from mediators produced from complex interaction of multiple inflammatory cells, was assessed on 20 protocol biopsies obtained from 6 patients, of which 4 patients had 4 biopsies and 2 patients had 1 biopsy. Results: Kidney volume was obtained from 51 ultrasound studies performed up to 74 months after transplant. Kidney volume generally increased and eGFR rose over time after the transplant, with 23% patients achieving an eGFR of >75 mL/min/1.73 m2 at 3 months posttransplant. The remainder achieved an eGFR >75 mL/min/1.73 m2 over the ensuing 3 years. Interstitial fibrosis noted on biopsies appeared to foreshadow an eventual reduction in kidney volume. Limitations: Retrospective study, possible selection bias, single-center experience. Conclusions: The kidney en bloc allografts increased in size after transplantation, with associated improved kidney function. Chronic damage to the graft, from interstitial fibrosis and tubular atrophy, resulted in long-term reduction in kidney volume.

Introduction: Valid prediction models or predictors of disease progression in children and young patients with autosomal dominant polycystic kidney disease (ADPKD) are lacking. Although total kidney volume (TKV) and Mayo imaging classification are generally used to predict disease progression in patients with ADPKD, it remains unclear whether germline mutation types are associated with these factors. We therefore investigated the association between mutation type and TKV and Mayo imaging classification among patients with ADPKD. Methods: A total of 129 patients with ADPKD who underwent genetic analyses were enrolled in the study. The associations between the severity of PKD (TKV ≥ 1000 ml and Mayo classes 1C–1E) and the PKD1 mutation types (nonsense mutation, frameshift or splicing mutation, and substitution) were evaluated. Results: Among the mutation types, only PKD1 splicing/frameshift mutation had significant associations with TKV ≥ 1000 ml in sex-adjusted and multivariable logistic analyses. Similarly, only the PKD1 splicing/frameshift mutation was significantly associated with Mayo 1C–1E in sex-adjusted and multivariable logistic analyses. PKD1 nonsense mutation, PKD1 substitution, or PKD1 mutation position had no significant association with TKV ≥ 1000 ml or Mayo 1C–1E. Conclusion: Kidney cyst severity differs according to the mutation types in PKD1. Patients with PKD1 splicing mutations or PKD1 frameshift mutations are associated with TKV ≥ 1000 ml or Mayo 1C–1E. Detailed assessment of mutation types may be useful for predicting renal prognosis in patients with ADPKD and may especially contribute to the care of a high-risk group of children with ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) eventually leads to end stage renal disease (ESRD) with an increase in size and number of cysts over time. Progression to ESRD has previously been shown to correlate with total kidney volume (TKV). An accurate and relatively simple method to perform measurement of TKV has been difficult to develop. We propose a semi-automated approach of calculating TKV inclusive of all cysts in ADPKD patients based on b0 images relatively quickly without requiring any calculations or additional MRI time. Our purpose is to evaluate the reliability and reproducibility of our method by raters of various training levels within the environment of an advanced 3D viewer. Thirty patients were retrospectively identified who had DWI performed as part of 1.5T MRI renal examination. Right and left TKVs were calculated by five radiologists of various training levels. Interrater reliability (IRR) was estimated by computing the intraclass correlation (ICC) for all raters. ICC values calculated for TKV measurements between the five raters were 0.989 (95% CI = (0.981, 0.994), p < 0.01) for the right and 0.961 (95% CI = (0.936, 0.979), p < 0.01) for the left. Our method shows excellent intraclass correlation between raters, allowing for excellent interrater reliability.

Organ volume measurements are a key metric for managing ADPKD (the most common inherited renal disease). However, measuring organ volumes is tedious and involves manually contouring organ outlines on multiple cross-sectional MRI or CT images. The automation of kidney contouring using deep learning has been proposed, as it has small errors compared to manual contouring. Here, a deployed open-source deep learning ADPKD kidney segmentation pipeline is extended to also measure liver and spleen volumes, which are also important. This 2D U-net deep learning approach was developed with radiologist labeled T2-weighted images from 215 ADPKD subjects (70% training = 151, 30% validation = 64). Additional ADPKD subjects were utilized for prospective (n = 30) and external (n = 30) validations for a total of 275 subjects. Image cropping previously optimized for kidneys was included in training but removed for the validation and inference to accommodate the liver which is closer to the image border. An effective algorithm was developed to adjudicate overlap voxels that are labeled as more than one organ. Left kidney, right kidney, liver and spleen labels had average errors of 3%, 7%, 3%, and 1%, respectively, on external validation and 5%, 6%, 5%, and 1% on prospective validation. Dice scores also showed that the deep learning model was close to the radiologist contouring, measuring 0.98, 0.96, 0.97 and 0.96 on external validation and 0.96, 0.96, 0.96 and 0.95 on prospective validation for left kidney, right kidney, liver and spleen, respectively. The time required for manual correction of deep learning segmentation errors was only 19:17 min compared to 33:04 min for manual segmentations, a 42% time saving (p = 0.004). Standard deviation of model assisted segmentations was reduced to 7, 5, 11, 5 mL for right kidney, left kidney, liver and spleen respectively from 14, 10, 55 and 14 mL for manual segmentations. Thus, deep learning reduces the radiologist time required to perform multiorgan segmentations in ADPKD and reduces measurement variability. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) eventually leads to end stage renal disease (ESRD) with an increase in size and number of cysts over time. Progression to ESRD has previously been shown to correlate with total kidney volume (TKV). An accurate and relatively simple method to perform measurement of TKV has been difficult to develop. We propose a semiautomated approach of calculating TKV inclusive of all cysts in ADPKD patients based on b0 images relatively quickly without requiring any calculations or additional MRI time. Our purpose is to evaluate the reliability and reproducibility of our method by raters of various training levels within the environment of an advanced 3D viewer. Thirty patients were retrospectively identified who had DWI performed as part of 1.5T MRI renal examination. Right and left TKVs were calculated by five radiologists of various training levels. Interrater reliability (IRR) was estimated by computing the intraclass correlation (ICC) for all raters. ICC values calculated for TKV measurements between the five raters were 0.989 (95% CI = (0.981, 0.994), p < 0.01) for the right and 0.961 (95% CI = (0.936, 0.979), p < 0.01) for the left. Our method shows excellent intraclass correlation between raters, allowing for excellent interrater reliability. [ABSTRACT FROM AUTHOR]

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., (Published by Elsevier Inc.)

Background: Pediatric nephrologists use kidney length and kidney volume z-scores to longitudinally assess normal nephron endowment. However, most radiologists only report kidney length. Agreement between kidney length and kidney volume z-scores in children has been understudied. This study aims to assess agreement between kidney length and kidney volume z-scores in children. Methods: This novel cross-sectional cohort study prospectively followed prematurely born babies from a large specialized prematurity follow-up center. A healthy control group matched the cases by age and sex and was recruited from schools. Children were assessed for kidney length and kidney volumes at age 5 by three independent ultrasonographers. All measurements were performed in triplicate. Detailed anthropometry, blood pressure, and kidney function were also obtained. Age-independent z-scores were calculated for all parameters according to Scholbach and Weitzel and compared using descriptive statistics. Results: We studied 89 premature patients (median 32 weeks gestational age) and 33 healthy controls (median 38 weeks gestational age). There were 732 determinations of kidney length, width, and thickness. The mean z-score of the right kidney length was 0.65 ± 0.08 (SEM) compared with 0.88 ± 0.08 of the left kidney length (p = 0.0003, two-sided paired t test). The squared correlation coefficient for kidney volume to kidney length was 0.32 (p < 0.0001). Bland and Altman analysis revealed considerable bias with − 1.36 ± 0.76 standard deviations and 95% limits of agreement from − 2.83 to − 0.16. Conclusion: Reporting only kidney length results in significant overestimation of age-independent z-scores. Based on our findings, consideration to measuring all kidney dimensions may be more appropriate. [ABSTRACT FROM AUTHOR]

Kidney volume is an essential biomarker for a number of kidney disease diagnoses, for example, chronic kidney disease. Existing total kidney volume estimation methods often rely on an intermediate kidney segmentation step. On the other hand, automatic kidney localization in volumetric medical images is a critical step that often precedes subsequent data processing and analysis. Most current approaches perform kidney localization via an intermediate classification or regression step. This paper proposes an integrated deep learning approach for (i) kidney localization in computed tomography scans and (ii) segmentation-free renal volume estimation. Our localization method uses a selection-convolutional neural network that approximates the kidney inferior-superior span along the axial direction. Cross-sectional (2D) slices from the estimated span are subsequently used in a combined sagittal-axial Mask-RCNN that detects the organ bounding boxes on the axial and sagittal slices, the combination of which produces a final 3D organ bounding box. Furthermore, we use a fully convolutional network to estimate the kidney volume that skips the segmentation procedure. We also present a mathematical expression to approximate the ‘volume error’ metric from the ‘Sørensen–Dice coefficient.’ We accessed 100 patients’ CT scans from the Vancouver General Hospital records and obtained 210 patients’ CT scans from the 2019 Kidney Tumor Segmentation Challenge database to validate our method. Our method produces a kidney boundary wall localization error of ~2.4mm and a mean volume estimation error of ~5%. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to use the volume of the graft as an adjunct tool for better decision making. Methods: Kidney transplanted patients with acute azotemia and documented volume and finally a biopsy were enrolled in this study‌. Graft volumes between rejected patients (antibody-mediated rejection {AMR} and cell - mediated rejection {CMR}) and ‌non rejected but azotemic patients were compared. Results: A total of 76 patients were enrolled in this study ‌(45 case and 31 control‌). 53.3% of the case group were‌ (AMR)‌ and 46.7% belonged to ‌(CMR). There was no difference between kidney volume according to age or sex. But the case group had a significantly bigger volume than controls (253.09 cm3 and 186.45 cm3; p< 0.001). In addition, there was a significant difference between the volumes of AMR kidneys with CMR and controls ‌(286.24+66.70‌, 224.08+76.79 and 186.95+39.92; P=0.003 and p

Renal imaging is widely used in the assessment of surrogate markers of nephron mass correlated to renal function. Autopsy studies have tested the validity of various imaging modalities in accurately estimating "true" nephron mass. However, in vivo assessment of nephron mass has been largely limited to kidney volume determination by ultrasonography (US) in pediatric populations. Practical limitations and risks create challenges in incorporating more precise 3D volumetric imaging, like magnetic resonance imaging (MRI), and computed tomography (CT) technologies, compared to US for routine kidney volume assessment in children. Additionally, accounting for structural anomalies such as hydronephrosis when estimating renal parenchymal area in congenital anomalies of the kidney and urinary tract (CAKUT) is important, as it correlates with chronic kidney disease (CKD) progression. 3D imaging using CT and MRI has been shown to be superior to US, which has traditionally relied on 2D measurements to estimate kidney volume using the ellipsoid calculation. Recent innovations using 3D and contrast-enhanced US (CEUS) provide improved accuracy with low risk. Indexing kidney volume to body surface area in children is an important standard that may allow early detection of CKD progression in high-risk populations. This review highlights current understanding of various imaging modalities in assessing nephron mass, discusses applications and limitations, and describes recent advances in the field of imaging and kidney disease. Although renal imaging has been a long-standing, essential tool in assessing kidney disease, innovation and new applications of established technologies provide important tools in the study and management of kidney disease in children. [ABSTRACT FROM AUTHOR]

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. 117 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yilmaz, Saygili, Canpolat, Akgun-Dogan, Yuruk Yildirim, Cicek-Oksuz, Oner, Aksu, Akyel, Oguzhan-Hamis, Dursun, Yavuz, Cicek, Akinci, Karabag Yilmaz, Agbas, Nayir, Konukoglu, Kurugoglu, Sever and Caliskan.)

Summary: Kidney volume has been proven to be a surrogate marker of nephron mass and renal function. We studied 190 donor and recipient pairs undergoing living donor kidney transplantation at our institution during 9 years. Different metrics of donor kidney volume (DKV) were explored: alone or indexed to recipient's anthropometry, as body surface area (BSA). DKV/BSA (min. 49.7; P33rd 77.7; P67th 95.3; max. 176 cm3/m2) was chosen given its higher correlation with eGFR at 1 year, and recipients were divided according to its tertiles (T). The eGFR at 1 year was lower in T1, when compared with T2 (P = 0.015) and T3 (P < 0.001). In a multivariable model, a regression spline revealed that a DKV/BSA lower than 80 was significantly associated with an eGFR at 1 year <60. In the first 6 years, the overall annual eGFR slope was −0.90 ml/min/year. Acute rejection occurred in 19%, 11%, and 0% of patients in T1, T2, and T3, respectively (P < 0.001). DKV/BSA increased stepwise from cellular‐ (n = 12) to antibody‐mediated (n = 7) AR cases and to those without AR (n = 171; P = 0.002; no AR versus cellular AR). Lower DKV/BSA ratio was associated with significantly worse graft function and higher incidence of AR. Hence, it can be a tool for better selection of donors in order to improve graft outcomes, particularly in the setting of multiple potential living donors or kidney paired exchange programs. [ABSTRACT FROM AUTHOR]

The donors' estimated glomerular filtration rate (eGFR) after living nephrectomy has been a concern, particularly in donors with smaller kindeys. Therefore, we developed this retrospective observational study in 195 donors to determine the ability remaining kidney volume indexed to weight (RKV/W) to predict eGFR at 1 year through multivariate linear regression and to explore this relationship between annual eGFR change from 1 to 4 years postdonation evaluated by a linear mixed model. Comparing RKV/W tertiles (T1, T2, T3), RKV/W was a good predictor of 1‐year eGFR which was significantly better in T3 donors. Gender, predonation eGFR, and RKV/W were independent predictors of eGFR at 1‐year. In a subgroup with predonation eGFR < 90mL/min/1.73 m2, a significant prediction of eGFR < 60mL/min/1.73 m2 was detected in males with RKV/W ≤ 2.51cm3/kg. Annual eGFR (ml/min/year) change from 1 to 4 years was + 0.77. RKV/W divided by tertiles (T1–T3) was the only significant predictor: T2 and T3 donors had an annual eGFR improvement opposing to T1. RKV/W was a good predictor of eGFR at 1 year, independently from predonation eGFR. A higher RKV/W was associated with improved eGFR at 1 year. A decline in eGFR on the four years after surgery was only noticeable in donors with RKV/W ≤ 2.13cm3/kg. [ABSTRACT FROM AUTHOR]

The variable disease course of autosomal dominant polycystic kidney disease (ADPKD) makes it important to develop biomarkers that can predict disease progression, from a patient perspective and to select patients for renoprotective treatment. We therefore investigated whether easy-to-measure urinary biomarkers are associated with disease progression and have additional value over that of conventional risk markers. Methods: At baseline, inflammatory, glomerular, and tubular damage markers were measured in 24-hour urine collections (albumin, IgG, kidney injury molecule−1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), β2 microglobulin (β2MG), heart-type fatty acid binding protein (HFABP), macrophage migration inhibitory factor (MIF), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein−1 (MCP-1). Disease progression was expressed as annual change in estimated glomerular filtration rate (eGFR, Chronic Kidney Disease EPIdemiology equation), measured glomerular filtation rate (mGFR, using 125I-iothalamate), or height-adjusted total kidney volume (htTKV). Multivariable linear regression was used to assess associations of these markers independent of conventional risk markers. Results: A total of 104 ADPKD patients were included (40 ± 11 years, 39% female, eGFR 77 ± 30, mGFR 79 ± 30 ml/min per 1.73 m2 and htTKV 852 [510−1244] ml/m). In particular, β2MG and MCP-1 were associated with annual change in eGFR, and remained associated after adjustment for conventional risk markers (standardized β = −0.35, P = 0.001, and standardized β = −0.29, P = 0.009, respectively). Adding β2MG and MCP-1 to a model containing conventional risk markers that explained annual change in eGFR significantly increased the performance of the model (final R2 = 0.152 vs. 0.292, P = 0.001). Essentially similar results were obtained when only patients with an eGFR ≥ 60 ml/min per 1.73 m2 were selected, or when change in mGFR was studied. Associations with change in htTKV were less strong. Conclusion: Urinary β2MG and MCP-1 excretion were both associated with GFR decline in ADPKD, and had added value beyond that of conventional risk markers. These markers therefore have the potential to serve as predictive tools for clinical practice.

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients with differing baseline characteristics. Methods The ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to the overall TEMPO 3:4 study population. Results A cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant patient profiles. Conclusions The ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical judgement, it has the potential to support decision-making in research and clinical practice.

Background: We carried out a study to determine the impact of prematurity on kidney development in the first 2 years of life. Methods: In this prospective study, extremely preterm neonates (gestation < 28 weeks) were recruited and underwent assessments at 6, 12, and 24 months of age. A cohort of neonates born term were also recruited and followed up for 24 months. The primary outcomes measured in this study were total kidney volume (TKV) and estimated glomerular filtration rate (eGFR); albuminuria and blood pressure measurements (all provided as mean (standard deviation)) were the secondary outcomes. Results: Fifty-three premature and 31 term neonates (control) were recruited. At the age of 24 months (corrected age), infants born preterm had significantly smaller TKV (56.1 (9.4) vs. 64.8 (10.2) mL; P = 0.006). There was no difference in eGFR. These preterm infants were smaller (11.25 (1.53) vs. 12.9 (1.8) kg; P = 0.002) and shorter (83.8 (3.0) vs. 86.3 (3.4) cm; P = 0.02) when compared with the control group. At 6, 12, and 18 months respectively, preterm infants had, relative to their height, significantly smaller kidney volumes (0.54 (0.1) vs. 0.59 (0.1) mL/cm, P = 0.05; 0.61 (0.1) vs.0.71 (0.1) mL/cm, P = 0.003; and 0.67 (0.1) vs.0.76 (0.1) mL/cm, P = 0.006). Conclusions: Relative to body length, TKV in premature infants is smaller. Since length reflects adult body proportions more accurately than BSA, TKV to height ratio may be a more important measure in the child. Despite smaller TKV (and therefore fewer nephrons), infants born prematurely achieve similar eGFRs in the first 24 months of life, probably due to single-nephron hyperfiltration. [ABSTRACT FROM AUTHOR]

Parenchymal damage and renal function impairment following percutaneous nephrolithotomy (PCNL) are of great concern. This study aims to evaluate post-operative changes in renal volume after PCNL. We retrospectively analyzed baseline and post-PCNL CT images from 25 eligible patients from a single tertiary care center. All CT imaging was reviewed using 3D planimetry software (3D Splicer®, Version 4.0). Segmentation was utilized to obtain total kidney volume (TKV), total kidney surface area, total stone surface area, and total stone volume. Wilcoxon signed-rank test was used for pair analysis, and univariate and multivariable analyses were performed to examine the relationships between clinical and planimetry data and renal volume loss. The median age of the cohort was 62 years, with the majority of the patients having undergone a previous PCNL (52.0%). The median TKV (cm3) pre- and post-PCNL were 225.25 and 178.09, respectively (p = 0.001), with average volume decline of 21%. While there was a statistically significant kidney volume loss in our cohort, there was no difference between pre- and post-operative serum creatinine (mg/dL): 0.93 and 0.94 (p = 0.696), respectively. Multivariable analysis showed a higher TKV loss with a larger kidney stone surface area (OR 1.002, CI 1–1.003, p = 0.035), while younger age was found to be protective (OR 0.791, CI 0.587–0.925 p = 0.028). Patients with previous history of PCNL experiences a more pronounced TKV loss (53.77 cm3, p = 0.031), as compared to PCNL naïve patients (13.05 cm3, p = 0.224). Our study consistently revealed a decrease in TKV following PCNL. Furthermore, among patients with larger stone surface areas, and history of previous PCNL there was an increase in the loss of TKV after the procedure. [ABSTRACT FROM AUTHOR]

Background: Renal length, volume, and parenchymal thickness are important clinical parameters, yet data concerning the accuracy and reproducibility of ultrasound (US)-based renal length and volume assessment in patients with chronic kidney disease (CKD) are scarce. Purpose: To establish whether renal length, volume, and parenchymal thickness can be reliably measured with renal US in patients with CKD. Material and Methods: All participants underwent renal US, immediately followed by 3-T magnetic resonance imaging (MRI). Renal length, width, transverse diameter, and parenchyma thickness were measured with both methods; renal volume was calculated using the ellipsoid formula. A total of 45 patients with CKD (eGFR [mean ± SD] 57.4 ± 4.4 mL/min/1.73 m2) and 46 participants without CKD (eGFR 97.0 ± 2.4 mL/min/1.73 m2) were included. Results: US-measured renal length correlated strongly with MRI-measured renal length in no-CKD patients (Spearman's r = 0.83 and 0.85 for the right and left kidney, respectively; P < 0.005) and CKD patients (r = 0.89 and 0.92 for the right and left kidney, respectively; P < 0.005). There was a significant but weaker correlation between MRI- and US-measured right and left renal volume (r = 0.72, P < 0.005) in no-CKD (r = 0.74 and r = 0.72, respectively; for both: P < 0.005) and CKD patients (r = 0.83 and 0.85, P < 0.005). Weak to moderate correlations were found for parenchyma thickness for the right (CKD group: r = 0.29, no-CKD: r = 0.23; for both: P < 0.05) and left kidney (CKD: r = 0.52, no-CKD group: r = 0.37, P < 0.05). Both intra-observer (Pearson's correlations of 0.82 for the right and 0.89 for the left kidney) and inter-observer (Lin's correlation coefficient of 0.90 for the right and 0.82 for the left kidney) reproducibility of US-assessed renal length was high. Conclusions: US-based assessment of renal length in CKD patients is comparable to MRI measures. Both intra- and inter-observer reproducibility of US-assessed renal length in CKD patients are high. Measurements of US renal volume and parenchymal thickness should, however, be interpreted with caution. [ABSTRACT FROM AUTHOR]

To propose a rapid multi-slice T 1 measurement method using time-resolved imaging of contrast kinetics (TRICKS) and a semi-automated image processing algorithm for comprehensive assessment murine kidney function using dynamic contrast-enhanced MRI (DCE-MRI). A multi-slice TRICKS sampling scheme was implemented in an established rapid T 1 measurement method. A semi-automated image-processing scheme employing basic image processing techniques and machine learning was developed to facilitate image analysis. Reliability of the multi-slice technique in measuring renal perfusion and glomerular filtration rate (GFR) was tested in normal mice (n = 7 for both techniques) by comparing to the validated single-slice technique. Utility of this method was demonstrated on mice after either sham surgery (n = 7) or induction of unilateral renal artery stenosis (RAS, n = 8). Renal functional parameters were extracted using a validated bi-compartment model. The TRICKS sampling scheme achieved an acceleration factor of 2.7, allowing imaging of eight axial slices at 1.23 s/scan. With the aid of the semi-automated scheme, image analysis required under 15-min for both kidneys per mouse. The multi-slice technique yielded renal perfusion and GFR values comparable to the single-slice technique. Model-fitted renal parameters successfully differentiated control and stenotic mouse kidneys, including renal perfusion (706.5 ± 164.0 vs. 375.9 ± 277.9 mL/100 g/min, P = 0.002), blood flow (1.6 ± 0.4 vs. 0.7 ± 0.7 mL/min, P < 0.001), and GFR (142.9 ± 17.9 vs. 58.0 ± 42.8 μL/min, P < 0.001). The multi-slice TRICKS-based DCE-MRI technique, with a semi-automated image processing scheme, allows rapid and comprehensive measurement of murine kidney function. [ABSTRACT FROM AUTHOR]

Background: Reduced kidney volume (KV) following prematurity is a proxy for reduced nephron number and is associated with the development of hypertension and end-stage renal disease in adults. We investigated whether extreme prematurity affects KV, function, and blood pressure in school-aged children and if nephrocalcinosis (NC) developed during the neonatal period had additional effects. Methods: We investigated 60 children at a mean age of 7.7 years: 20 born extremely preterm (EPT < 28 weeks gestational age with NC (NC+)), 20 born EPT without NC (NC−), and 19 born as full-term infants (control). We measured KV by ultrasound, collected blood and urine samples to evaluate renal function, and measured office and 24-h ambulatory blood pressure (ABPM). Results: Children born EPT had significantly smaller kidneys (EPT (NC+ NC−) vs control (estimated difference, 11.8 (CI − 21.51 to − 2.09 ml), p = 0.018) and lower but normal cystatin C–based glomerular filtration rate compared with control (estimated difference, − 10.11 (CI − 0.69 to − 19.5), p = 0.035). KV and function were not different between NC+ and NC− groups. Change in KV in relation to BSA (KV/BSA) from the neonatal period to school age showed significantly more EPT children with neonatal NC having a negative evolution of KV (p = 0.01). Blood pressure was normal and not different between the 3 groups. Fifty percent of EPT had a less than 10% day-to-night decline in ABPM. Conclusions: Kidney growth and volume is affected by EPT birth with NC being a potential aggravating factor. Circadian blood pressure regulation seems abnormal in EPT-born children. [ABSTRACT FROM AUTHOR]

Diabetes is considered one of the major causes of chronic kidney disease (CKD), affecting renal blood vessels and nerves. Diagnosis of CKD by traditional biochemical serum and blood analyses is insufficient and insensitive, thus requiring the development of a more robust technique. This novel study aims to propose a new method for the accurate diagnosis of CKD, quantification of kidney damage, and its prognosis by physicians by measuring the kidney volume on computed tomography (CT). In total, 251 patients were enrolled in this retrospective study. They were divided into four groups: control, patients having diabetes, patients having CKD, and patients having both diabetes and CKD. Results showed that kidney volume correlated negatively with both GFR and HbA1C on CT images, in addition to decreasing faster in males than females. Moreover, HbA1C was shown to correlate positively with creatinine and negatively with GFR. Finally, GFR was more robust than creatinine when correlated with age. The association between kidney volume with GFR and HbA1c can be used to accurately anticipate kidney volume in established CKD on CT scan, especially in resource-poor settings. Furthermore, HbA1C can serve as a powerful biomarker for studying renal function in diabetic CKD patients as it correlates with creatinine and GFR.