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Alport syndrome ( ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing ( NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/ A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/ A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation ( COL4A5) combined with an inherited mutation ( COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members. [ABSTRACT FROM AUTHOR]

This paper considers different cooling systems and investigates the most promising alternatives when solar energy is to be used to supply the cooling demand. All the systems are evaluated during a summer cooling season by the energetic and economic point of view by dynamic simulation for two different climates. For Milan (Cfb climate) the highest OSE (overall system efficiency) is reached by LiBr (lithium-bromide) double effect absorption chiller driven by parabolic through collector (0.53). In terms of the collecting surface area, the best systems for Milan feature 0.08 m2 MJ−1 per day both for electric system (mono-crystalline photovoltaic coupled to water cooled chiller) and thermal system (PTC (parabolic trough collectors) coupled to double effect water-LiBr absorption chiller). Southern latitudes like Trapani (Csa climate) allow a quite better performance for thermal solar cooling solutions. The NPV (net present worths) of electric solar cooling solutions are favorable with respect to the traditional solution and the DPV (discounted payback periods) are all lower than the period of economic analysis above all for water cooled chillers. Finally a sensitivity analysis of the specific investment cost (€ MJ−1 per day) is carried out regarding the investment cost of collectors, the solar ratio and the interest rate. [ABSTRACT FROM AUTHOR]

Abstract Red or variegated chicory (Cichorium intybus L., 2n = 2x = 18) native to, and very extensively cultivated in north-eastern Italy as a leafy vegetable, locally called ‘radicchio’, includes different types which represent valuable high-quality crops. The five major types of radicchio cultivated in the Veneto region were investigated by polymerase chain reaction (PCR)-derived markers. The experimental material was represented by two outbred populations (one of ‘Variegato di Castelfranco’ (CF) and one of ‘Rosso di Verona’ (VR)) and by eight inbred lines (three of early ‘Rosso di Treviso’ (TVP), three of late ‘Rosso di Treviso’ (TVT) and two of ‘Rosso di Chioggia’ (CH)). A total of 96 individual plant DNAs and 16 bulked DNAs of six plants each were assayed. The different types were well distinguished from one another if analysed by means of bulks using amplified fragment length polymorphism markers at the population level, while they were not if analysed at the individual level using random amplified polymorphic DNA, inter-simple sequence repeat and Arbitrarily Primed (AP)-PCR markers. The genetic variation was shown to be much higher within types than between types. This result suggests that, in each radicchio type, populations produced by breeders through controlled intercrossing (VR and CF) or repeated selfing (TVP, TVT and CH) conserved their well-separated gene pools over the years. The setting up of a molecular reference system seems to be feasible and suitable both for the precise identification of the single types of radicchio and for the evaluation of the extent of natural hybridization that can occur between different types. [ABSTRACT FROM AUTHOR]

The evaluation of estimated GFR (eGFR) is a pivotal staging step in patients with chronic kidney disease (CKD), and renal ultrasound plays an important role in diagnosis, prognosis and progression of CKD. The interaction between histopathological diagnosis and ultrasound parameters in eGFR determination has not been fully investigated yet. The study examined the results of native kidney biopsies performed in 48 Italian centers between 2012 and 2020. The primary goal was if and how the histopathological diagnosis influences the relationship between ultrasound parameters and eGFR. After exclusion of children, patients with acute kidney injury and patients without measure of kidney length or parenchymal thickness, 2795 patients have been selected for analysis. The median values were 52 years for patient age, 11 cm for bipolar kidney diameter, 16 mm for parenchymal thickness, 2.5 g/day for proteinuria and 70 ml/min/1.73 m 2 for eGFR. The bipolar kidney diameter and the parenchymal thickness were directly related with eGFR values (R square 0.064). Diabetes and proteinuria were associated with a consistent reduction of eGFR, improving the adjusted R square up to 0.100. Addition of histopathological diagnosis in the model increased the adjusted R square to 0.216. There is a significant interaction between histopathological diagnosis and longitudinal kidney diameter (P 0.006). Renal bipolar length and parenchymal thickness are directly related with eGFR. The magnitude of proteinuria and histopathological kidney diagnosis are associated with eGFR. The relationship between kidney length and the level of eGFR depends on the nature of the kidney disease., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format. Informed consent: Informed consent was obtained from all the enrolled patients or their parents/legal guardians., (© 2024. The Author(s).)

Background: Systemic steroids are recommended for patients with IgA nephropathy (IgAN) and proteinuria. However, there are concerns about their safety due to an excess of serious adverse events (SAEs) in previous randomised trials. This study evaluates the incidence of SAEs in IgAN patients receiving different treatment regimens in clinical practice., Methods: Multicentre, retrospective, observational cohort study of 1209 patients (M/F: 864/345, mean age: 41.73 ± 14.92 years) with biopsy-proven IgAN treated with renin angiotensin system (RAS) inhibitors (RASI) (n = 285), intravenous + oral steroids (n = 633), oral steroids (n = 99), steroids + immunosuppressants (n = 192)., Results: A total of 119 (9.8%) adverse events were reported, of which 67 (5.5%) were considered treatment-emergent, and 36 (2.9%) were SAEs (n = 23, 63.8% were infections). One patient died due to sepsis. A significant association was observed between AEs and immunosuppression [8 (2.8%) in RASI, 60 (9.4%) in steroids + immunosuppressants, 14 in oral steroids (14.1%) and 37 pts (19.2%) in steroids + immunosuppressants (p < 0.01)], age and estimated glomerular filtration rate (eGFR), but not with proteinuria and sex. On multivariate analysis, only older age was associated with the occurrence of SAEs., Conclusions: According to our findings, the incidence of SAEs during therapy with steroids alone or associated with immunosuppressors is lower in everyday clinical practice than in randomised clinical trials., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Introduction: Primary focal segmental glomerular sclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty., Methods: We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24-hour proteinuria <3.5 g and <50% compared with baseline, stable estimated glomerular filtration rate)., Results: A total of 31 patients were followed for at least 12 months; further follow-up (median 17 months, interquartile range [IQR] 15-33.5) was available for 11. At first RTX administration, median creatinine and 24-hour proteinuria were 1.17 mg/dl (IQR 0.83-1.62) and 5.2 g (IQR 3.3-8.81), respectively. Response rate at 3, 6, and 12 months was 39%, 52%, and 42%, respectively. In the first 12 months, creatinine level remained stable whereas proteinuria and serum albumin level improved, with an increase in the proportion of patients tapering other immunosuppressants. There were 6 patients who were retreated with RTX within 12 months, either for proteinuria increase or refractory disease; only the 2 responders to the first RTX course experienced a further response. At univariate analysis, 6-month response was more frequent in steroid-dependent patients (odds ratio [OR] 7.7 [95% CI 1.16-52.17]) and those with proteinuria <5 g/24 h (OR 8.25 [1.45-46.86]). During long-term follow-up, 4 of 5 responders at 12 months maintained a sustained response, either without further immunosuppression (2 of 4) or with pre-emptive RTX (2 of 4); 1 relapsed and responded to RTX retreatment., Conclusion: RTX may be an option in primary FSGS, especially in steroid-dependent patients, with 24-hour proteinuria <5 g and previously responders to RTX. Optimal long-term management for responders is unclear, with some patients experiencing sustained remission and others requiring RTX retreatment, either preemptive or after rising proteinuria., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Bone morbidity remains a major problem even after successful renal transplantation. We investigated the role of calcium-sensing receptor (CaSR) polymorphisms and 25-hydroxyvitamin D levels on the persistence of secondary hyperparathyroidism (SHPT) and their relationships with vertebral fractures (VFx) in 125 renal allograft recipients transplanted 44 +/- 23 months before. All patients underwent evaluation of the main biochemical parameters of calcium metabolism as well as vertebral and femoral bone density. In 87 patients, CaSR polymorphisms (A986S, R990G, and Q1011E) also were assessed. X-ray images of the lateral spine were obtained in 102 subjects to perform vertebral morphometry. High parathyroid hormone (PTH) and 25-hydroxyvitamin D lower than 80 nmol/L were found in 54% and 97% of patients, respectively, with 40% of these showing vitamin D levels lower than 30 nmol/L. VFx were detected in 57% of the subjects. After multiple adjustments, 25-hydroxyvitamin D, age, and hemodialysis duration, but not CaSR polymorphisms, were found to be significant predictors of high PTH, whereas age and time since transplant were positively related with lower 25-hydroxyvitamin D values. PTH and time since transplant were significantly associated with VFx. Patients with two or more VFx showed serum PTH levels 50% higher than patients without fractures. We therefore conclude that persistent SHPT is a very common feature after renal transplantation and that, unlike CaSR polymorphisms, low 25-hydroxyvitamin D is involved in its pathogenesis. High PTH levels, in turn, are associated with an increased VFx risk, which confirms the need for strategies aimed at lowering serum PTH in this setting as well., (Copyright 2010 American Society for Bone and Mineral Research.)

The authors examine a presentation to the Royal Academy of Sciences of Paris by L. Morin, French physician and meteorologist. In this communication the presence of "pores" in the stomach and the bladder, which would allow a quick elimination of the urines on the occasion of an abundant fluid intake.