The Role of PEC Progenitors in ADPKD Progression

BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease is a pathology mainly characterized by the progressive development and enlargement of cysts in each kidneys. Such as many adult epithelial tissue, renal tubule replaces damaged or death cells through the presence of stem/progenitor cells CD133(+)CD24(+) Obviously, in ADPKD the repair of damages is insufficient to block the disease, but renal stem cells could have a role in the pathology. In this study we investigate the localization and the involvement of cells CD133(+)CD24(+) in ADPKD progression. METHODS AND RESULTS: Two normal kidneys and two ADPKD kidneys were examined. CD133 and CD24 expression was investigated by confocal microscopy and immunoblotting. Renal tissue and cells were analyzed. CD133 and CD24 have the same localization in ADPKD tissues and in normal kidneys: a subset of epithelial cells (PEC) of Bowman' s capsule and luminal side of tubules. It is interesting that CD133(+) CD24(+) cells are statistically more represented in ADPKD tubules (p＜ 0.001) and in healthy glomeruli (p= 0.0016). Cysts express CD133 and CD24. CONCLUSIONS: Renal epithelial progenitors demonstrate to be involved in ADPKD pathogenesis but their role will have to be clarified and possibly managed to obtain improvement, or at least stabilization, of disease

MR quantitative biomarkers of non-alcoholic fatty liver disease: technical evolutions and future trends

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis as the earliest manifestation and hallmark, and ranges from benign fatty liver to non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is considered the reference standard for NAFLD diagnosis, grading and characterization, but it is limited by its invasiveness and observer-dependence. Among imaging surrogates for the assessment of hepatic steatosis, MR is the most accurate. (1)H MR spectroscopy (MRS) provides a quantitative biomarker of liver fat content (LFC) called proton density fat fraction (PDFF), but it is time-consuming, not widely available and limited in sample size. Several MR imaging (MRI) techniques, in particular fat suppression and in-opposed phase techniques, have been used to quantify hepatic steatosis, mainly estimating LFC from water and fat signal intensities rather than proton densities. Several technical measures have been introduced to minimize the effect of confounding factors, in particular a low flip angle, a multiecho acquisition and a spectral modeling of fat with multipeak reconstruction to address respectively T1 effect, T2* effect, and the multifrequency interference effects of fat protons, allowing to use MRI to estimate LFC based on PDFF. Tang et al. evaluated MRI-estimated PDFF, obtained by applying the above-mentioned technical improvements, in the assessment of hepatic steatosis, using histopathology as the reference standard. The identification of PDFF thresholds, even though to be further explored and validated in larger and more diverse cohorts, is useful to identify steatosis categories based on MRI-based steatosis percentages. MRI, with the new refined techniques which provide a robust quantitative biomarker of hepatic steatosis (PDFF) evaluated on the whole liver parenchyma, is a promising non-invasive alternative to LB as the gold standard for steatosis diagnosis and quantification

PAX2/Renal Coloboma Syndrome Expresses Extreme Intrafamilial Phenotypic Variability

Renal coloboma syndrome (RCS) is a disease characterized by kidney and ocular anomalies (kidney hypodysplasia and coloboma). RCS is caused, in half of the cases, by mutations in the paired box 2 (PAX2) gene, a critical organogenesis transcriptional factor. We report the case of a newborn with kidney hypodysplasia in a negative parental context where mother and father were phenotypically unaffected at the initial evaluation. The maternal family presented an important history of kidney disease with undefined diagnosis. Molecular characterization identified a PAX2 variant, classified as likely pathogenic. This variant segregates with the disease, and it was also found in the newborn, explaining his severe symptoms. It is noteworthy that the mother shows the same PAX2 variant, with an apparently negative kidney phenotype, displaying the possibility of an extreme variable expressivity of the disease. This feature suggests extreme caution in segregation analysis and family counseling of PAX2 pedigrees

Confidence Calibration for Deep Renal Biopsy Immunofluorescence Image Classification

With this work we tackle immunofluorescence classification in renal biopsy, employing state-of-the-art Convolutional Neural Networks. In this setting, the aim of the probabilistic model is to assist an expert practitioner towards identifying the location pattern of antibody deposits within a glomerulus. Since modern neural networks often provide overconfident outputs, we stress the importance of having a reliable prediction, demonstrating that Temperature Scaling (TS), a recently introduced re-calibration technique, can be successfully applied to immunofluorescence classification in renal biopsy. Experimental results demonstrate that the designed model yields good accuracy on the specific task, and that TS is able to provide reliable probabilities, which are highly valuable for such a task given the low inter-rater agreement

Subjective Symptoms in Magnetic Resonance Imaging Personnel: A Multi-Center Study in Italy

Introduction: Magnetic Resonance Imaging (MRI) personnel have significant exposure to static and low-frequency time-varying magnetic fields. In these workers an increased prevalence of different subjective symptoms has been observed. The aim of our study was to investigate the prevalence of non-specific subjective symptoms and of “core symptoms” in a group of MRI personnel working in different centers in Italy, and of possible relationships with personal and occupational characteristics.Methods: The occurrence of 11 subjective symptoms was evaluated using a specific questionnaire with 240 subjects working in 6 different Italian hospitals and research centers, 177 MRI health care and research personnel and 63 unexposed subjects employed in the same departments. Exposure was subjectively investigated according to the type of MRI scanner (≤1.5 vs. ≥3 T) and to the number of MRI procedures attended and/or performed by the personnel, even if no information on how frequently the personnel entered the scanner room was collected. The possible associations among symptoms and estimated EMF exposure, the main characteristics of the population, and job stress perception were analyzed.Results: Eighty-six percent of the personnel reported at least one symptom; drowsiness, headache, and sleep disorders were the most frequent. The total number of symptoms did not differ between exposed persons and controls. Considering the total number of annual MRI procedures reported by the personnel, no significant associations were found nor with the total number of symptoms, nor with “core symptoms.” Only subjects complaining of drowsiness also reported a significantly higher mean annual number of MRI procedures with ≤ 1.5 T scanners when compared with exposed subjects without drowsiness. In a multivariate model, subjects with a high level of perceived stress complained of more symptoms (p = 0.0002).Conclusions: Our study did not show any association between the occurrence of reversible subjective symptoms, including the more specific “core symptoms,” and the occupational exposure of MRI personnel to static and low-frequency time-varying magnetic fields. On the other hand, the role played by occupational stress appears to be not negligible. In further research in this field, measurements of EMF exposure should be considered

Molecular Imaging of Vascular Calcification with 18 F-Sodium-Fluoride in Patients Infected with Human Immunodeficiency Virus

18F-Sodium Fluoride (NaF) accumulates in areas of active hydroxyapatite deposition and potentially unstable atherosclerotic plaques. We assessed the presence of atherosclerotic plaques in 50 adult patients with HIV (HIV+) who had undergone two cardiac computed tomography scans to measure coronary artery calcium (CAC) progression. CAC and its progression are predictive of an unfavorable prognosis. Tracer uptake was quantified in six arterial territories: aortic arch, innominate carotid artery, right and left internal carotid arteries, left coronary (anterior descending and circumflex) and right coronary artery. Thirty-one patients showed CAC progression and 19 did not. At least one territory with high NaF uptake was observed in 150 (50%) of 300 arterial territories. High NaF uptake was detected more often in non-calcified than calcified areas (68% vs. 32%), and in patients without than in those with prior CAC progression (68% vs. 32%). There was no correlation between clinical and demographic variables and NaF uptake. In clinically stable HIV+ patients, half of the arterial territories showed a high NaF uptake, often in the absence of macroscopic calcification. NaF uptake at one time point did not correlate with prior progression of CAC. Prospective studies will demonstrate the prognostic significance of high NaF uptake in HIV+ patients

GREASE II. A phase II randomized, 12-month, parallel-group, superiority study to evaluate the efficacy of a Modified Atkins Diet in Autosomal Dominant Polycystic Kidney Disease patients

Introduction Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a condition that causes progressive renal function decline. Preclinical data suggest the presence of a profound metabolic derangement in ADPKD. Cystic cells shift their energy metabolism from oxidative phosphorylation to aerobic glycolysis, show inhibition of fatty acid oxidation and become glutamine and arginine dependent. Recent preclinical experiences have suggested beneficial effect in terms of reduction of cystic size, interstitial fibrosis and disease progression, targeting these deregulated metabolic pathways by ketosis induction. The dietetic approach to ADPKD, because of low cost and absence of toxicity, represents an interesting therapeutic strategy. Methods and analysis The protocol describes a phase II clinical trial that will evaluate the effect on Total Kidney Volume, safety and tolerability of a ketogenic diet in a selected ADPKD population. The trial will have, as secondary objective, the evaluation of the ability of the ketogenic diet to slow down the renal function decline. This will be a 12-month randomized, parallel group, two arm, superiority trial with 1:1 allocation to evaluate the efficacy of a Modified Atkins Diet protocol compared to a balanced normocaloric diet on 90 ADPKD patients. Dissemination The study results will be released to the patients and the medical community

Rethinking Chronic Kidney Disease in the Aging Population

The process of aging population will inevitably increase age-related comorbidities including chronic kidney disease (CKD). In light of this demographic transition, the lack of an age-adjusted CKD classification may enormously increase the number of new diagnoses of CKD in old subjects with an indolent decline in kidney function. Overdiagnosis of CKD will inevitably lead to important clinical consequences and pronounced negative effects on the health-related quality of life of these patients. Based on these data, an appropriate workup for the diagnosis of CKD is critical in reducing the burden of CKD worldwide. Optimal management of CKD should be based on prevention and reduction of risk factors associated with kidney injury. Once the diagnosis of CKD has been made, an appropriate staging of kidney disease and timely prescriptions of promising nephroprotective drugs (e.g., RAAS, SGLT-2 inhibitors, finerenone) appear crucial to slow down the progression toward end-stage kidney disease (ESKD). The management of elderly, comorbid and frail patients also opens new questions on the appropriate renal replacement therapy for this subset of the population. The non-dialytic management of CKD in old subjects with short life expectancy features as a valid option in patient-centered care programs. Considering the multiple implications of CKD for global public health, this review examines the prevalence, diagnosis and principles of treatment of kidney disease in the aging population