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

Benzothiadiazole-based conjugated polyelectrolytes for interfacial engineering in optoelectronic devices

Abstract Polar semiconducting polymers based on a conjugated polymer backbone endowed with chemically anchored polar groups on the side chains have proved to be particularly interesting as optimization layer at organic/cathode interface in optoelectronic devices. In particular, the pendant phosphonate groups impart water-alcohol solubility allowing easy solution processing, and improve electron injection thanks to both a favorable interfacial dipole of phosphonate groups and an intense coordination interaction between the phosphonate groups and Al cathode. In this work we synthesize alternating fluorene-benzothiadiazole copolymers by proposing a post-polymerization reaction to insert the phosphonate groups. Thanks to this approach it is possible to use standard Suzuki coupling conditions, simplifying the process of synthesis, purification and characterization. The polymer Poly[9,9-bis(6′-diethoxylphosphorylhexyl)-alt-benzothiadiazole] (P2), is tested in conventional organic solar cells as cathode interfacial layers showing, with respect to the control device, an increasing of all the photovoltaic parameters, with a final power conversion efficiency that reaches 5.35% starting from 4.6%. The same trend is observed for multilayered polymer light-emitting diodes with an external quantum efficiency of the P2-based PLED enhanced of 1.5 times with respect to the basic devices with bare Al cathode, and negligible roll-off efficiency. The synergic effects of energy gap modulation and of polar phosphonated pendant functionalities of P2 are compared with the corresponding fluorene-based polar homopolymer. Our results show that, not only a proper selection of side functionalities, but also the tailoring of the energy gap of cathode interfacial materials (CIMs) is a possible effective strategy to engineer cathode of different optoelectronic devices and enhance their performance

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

Prevalence, clinical course and outcomes of COVID-19 in peritoneal dialysis (PD) patients: a single-center experience

Introduction There are limited data on the effects of COVID-19 on peritoneal dialysis (PD) patients. This study aimed to describe the impact of COVID-19 on the PD population. Methods A monocentric retrospective observational study was conducted on 146 consecutive PD patients followed from January 2020 to March 2022 at the University Hospital of Modena, Italy. Results Twenty-seven (18.4%) PD patients experienced 29 episodes of SARS-CoV-2 infection, corresponding to an incidence rate of 0.16 episodes/patient-year. Median age of COVID-19 patients was 60.4 (interquartile range [IQR] 50.2-66.5) years. In unvaccinated patients (n. 9), COVID-19 was always symptomatic and manifested with fever (100%) and cough (77.7%). COVID-19 caused hospital admission of three (33.3%) patients and two (22.2%) died of septic shock. COVID-19 was symptomatic in 83.3% of vaccinated subjects (n.18) and manifested with fever (61.1%) and cough (55.6%). Hospital admission occurred in 27.8% of the subjects but all were discharged home. Median SARS-CoV-2 shedding was 32 and 26 days in the unvaccinated and vaccinated groups, respectively. At the end of the follow-up, COVID-19 triggered the shift from PD to HD in two subjects without affecting the residual renal function of the remaining patients. Overall, COVID-19 caused an excess death of 22.2%. COVID-19 vaccination refusal accounted for only 1.6% in this cohort of patients. Conclusion COVID-19 incident rate was 0.16 episodes/patient-year in the PD population. About one-third of the patients were hospitalized for severe infection. Fatal outcome occurred in two (7.4%) unvaccinated patients. A low vaccination refusal rate was observed in this population

COVID-19 Rapid Antigen Test Screening in Patients on Hemodialysis

Introduction. Patients receiving in-center hemodialysis are extremely vulnerable to COVID-19. It is unclear if routine screening of asymptomatic hemodialysis patients is an effective strategy to prevent COVID-19 outbreaks within the dialysis unit. Methods. We conducted a retrospective analysis of in-center hemodialysis patients who underwent bimonthly COVID-19 rapid antigen test screening from February 15(th) to December 26(th), 2021. Nasal rapid antigen testing was performed in all asymptomatic patients. All rapid antigen-positive tests were confirmed by RT-PCR nasopharyngeal swab. Besides universal rapid antigen screening, RT-PCR testing was conducted in all symptomatic patients and contacts of COVID-19 subjects. Results. Overall, 4079 rapid antigen tests were performed in 277 hemodialysis patients on chronic hemodialysis with a mean age of 68.4 +/- 14.6 years. Thirty-eight (0.9%) rapid antigen tests resulted positive. Only five (13.8%) positive-rapid antigen tests were also positive by RT-PCR testing. During the same period, 219 patients regularly screened by rapid antigen tests bimonthly underwent 442 RT-PCR nasopharyngeal swabs for clinical reasons. RT-PCR testing yielded a positive result in 13 (5.9%) patients. The time elapsed between PCR and the negative-rapid antigen test was 7.7 +/- 4.6 days (range 1.8-13.9 days). At the end of the follow-up, 6.4% of the population on in-center hemodialysis contracted COVID-19, and routine rapid antigen tests detected only 5 out of 18 (27.7%) COVID-19 cases. No outbreaks of COVID-19 were identified within the dialysis unit. Conclusion. Bimonthly rapid antigen screening led to the early diagnosis of COVID-19 in less than one-third of cases. The short incubation period of the new SARS-CoV-2 variants makes bimonthly test screening inadequate for an early diagnosis of COVID-19. More frequent tests are probably necessary to improve the utility of COVID-19 nasal rapid antigen test in patients on hemodialysis

Weekly Rapid Antigen Test Screening for COVID-19 in Patients on Hemodialysis

COVID-19 is a concerning issue among in-center hemodialysis (HD) patients. To prevent COVID-19 diffusion in our HD facility, weekly rapid nasal antigen test screening was performed for all asymptomatic patients on chronic HD. This study aimed to assess the performance of weekly rapid antigen test in detecting SARS-CoV-2 infection among asymptomatic patients receiving HD

Evaluation of the Classification Accuracy of the Kidney Biopsy Direct Immunofluorescence through Convolutional Neural Networks

Background and objectives: Immunohistopathology is an essential technique in the diagnostic workflow of a kidney biopsy. Deep learning is an effective tool in the elaboration of medical imaging. We wanted to evaluate the role of a convolutional neural network as a support tool for kidney immunofluorescence reporting. Design, setting, participants, & measurements: High-magnification ( 7400) immunofluorescence images of kidney biopsies performed from the year 2001 to 2018 were collected. The report, adopted at the Division of Nephrology of the AOU Policlinico di Modena, describes the specimen in terms of \u201cappearance,\u201d \u201cdistribution,\u201d \u201clocation,\u201d and \u201cintensity\u201d of the glomerular deposits identified with fluorescent antibodies against IgG, IgA, IgM, C1q and C3 complement fractions, fibrinogen, and \u3ba- and \u3bb-light chains. The report was used as ground truth for the training of the convolutional neural networks. Results: In total, 12,259 immunofluorescence images of 2542 subjects undergoing kidney biopsy were collected. The test set analysis showed accuracy values between 0.79 (\u201cirregular capillary wall\u201d feature) and 0.94 (\u201cfine granular\u201d feature). The agreement test of the results obtained by the convolutional neural networks with respect to the ground truth showed similar values to three pathologists of our center. Convolutional neural networks were 117 times faster than human evaluators in analyzing 180 test images. A web platform, where it is possible to upload digitized images of immunofluorescence specimens, is available to evaluate the potential of our approach. Conclusions: The data showed that the accuracy of convolutional neural networks is comparable with that of pathologists experienced in the field

Evaluation of a system for sorbent-assisted peritoneal dialysis in a uremic pig model

A system for sorbent-assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single-lumen peritoneal catheter with the regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by the maintenance of a high plasma-to-dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8-hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance the clearance of phosphate and organic waste solutes during the day. Uremic pigs (n = 3) were treated with the day- (n = 3) and nighttime system (n = 15) for 4-8 hr per treatment. Plasma clearance (Cl), MTAC, and total mass transport (MT) of urea, creatinine, phosphate, and potassium were compared with a static dwell (n = 28). Cl, MTAC, and MT of urea, creatinine, phosphate, and potassium were low in the pig as compared to humans due to the pig's low peritoneal transport status and could be enhanced only to a limited extent by SAPD treatment compared with a static dwell (nighttime system: Cl urea: ×1.5 (p = .029), Cl creatinine: ×1.7 (p = .054), Cl phosphate: ×1.5 (p = .158), Cl potassium: ×1.6 (p = .011); daytime system: Cl creatinine: ×2.7 (p = .040), Cl phosphate: ×2.2 (p = .039)). Sorbent-assisted peritoneal dialysis treatment in a uremic pig model is safe and enhances small solute clearance as compared to a static dwell. Future studies in humans or animal species with higher peritoneal transport should elucidate whether our SAPD system enhances clearance to a clinically relevant extent as compared to conventional PD