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Rationale & Objective: Alport syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS., Study Design: Retrospective cohort study., Setting & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA nephropathy (IgAN). Clinical, genetic, and imaging data were collected from medical records., Exposure: Cystic kidney phenotype evaluated by ultrasonography and defined as the presence of≥3 cysts in each kidney; demographic characteristics and estimated glomerular filtration rate (eGFR) at disease onset., Outcome: Cystic kidney phenotype in the AS and IgAN cohorts; time to chronic kidney disease (CKD) stage 3b and longitudinal changes in eGFR in the AS cohort., Analytical Approach: Logistic regression analysis to test independent strengths of associations of clinical/demographic features with the binary outcome of cystic phenotype. Survival analysis for the outcome of reaching CKD stage 3b and linear mixed models for changes in eGFR over time in the AS cohort., Results: We studied 108 patients with AS; 76 (70%) had a genetic diagnosis. Autosomal dominant AS was prevalent, accounting for 68% of patients with a genetic diagnosis. Cystic kidney phenotype was observed in 38% of patients with AS and was associated with normal-sized kidneys in all but 3 patients, who showed increased total kidney volume, mimicking autosomal dominant polycystic kidney disease. The prevalence of cystic kidney phenotype was significantly higher in patients with AS when compared with the group of patients with IgAN (42% vs 19%; P=0.002). Patients with the cystic kidney phenotype were older and had more marked reduction in eGFR than patients without cystic changes. Among patients with AS, the cystic phenotype was associated with older age and a faster decline eGFR., Limitations: Retrospective, single-center study., Conclusions: Cystic kidney phenotype is a common finding in AS. The cystic kidney phenotype is a common finding in AS, suggesting a possible role in cystogenesis for the genetic variants that cause this disease., Plain-Language Summary: Hematuria is the classic renal presentation of Alport syndrome (AS), a hereditary glomerulopathy caused by pathogenic variants of the COL4A3-5 genes. An atypical kidney cystic phenotype has been rarely reported in individuals with these variants. To determine the prevalence of kidney cysts, we performed abdominal ultrasonography in a large group of patients with AS and a comparison group of patients with another glomerular kidney disease, IgA nephropathy (IgAN). Multiple kidney cysts, usually with normal kidney volume, were found in 38% of patients with AS. A few patients' kidney volumes were large enough to mimic a different hereditary cystic kidney disease, autosomal dominant polycystic kidney disease. The overall prevalence of kidney cysts in AS was more than double that observed in the well-matched comparison group with IgAN. These findings emphasize the high prevalence of cystic kidney phenotype in AS, suggesting a likely association between the genetic variants that cause this disease and the development of kidney cysts., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, characterized by development and enlargement of kidney cysts, eventually leading to end-stage kidney disease (ESKD). Pathogenic variants in the PKD1 and PKD2 genes are the major cause of ADPKD; additional rare variants in the GANAB, DNAJB11, ALG5 and ALG9 genes have been found in a minority of ADPKD patients. More recently, a significant number of ADPKD families have been linked to monoallelic variants in the IFT140 gene., Methods: In this retrospective study, we tested the prevalence of the known causative genes of ADPKD-spectrum phenotype, including the PKD1, PKD2, GANAB, DNAJB11, ALG5, ALG and IFT140 genes, in a cohort of 129 ADPKD patients who consecutively underwent genetic testing in a single centre in Italy. Genetic testing utilized a combination of targeted next-generation sequencing, long-range polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification. Clinical evaluation was conducted through renal function testing and imaging features, including ultrasonography, computer tomography and magnetic resonance imaging., Results: Of the 129 enrolled patients, 86 (66.7%) had pathogenic variants in PKD1 and 28 (21.7%) in PKD2 , loss of function pathogenic variants in the IFT140 gene were found in 3 unrelated patients (2.3%), no pathogenic variants were found in other ADPKD genes and 12 patients (9.3%) remained genetically unresolved (ADPKD-GUR). Familial clinical and genetic screening of the index patients with ADPKD due to an IFT140 pathogenic variant (ADPKD- IFT140 ) allowed identification of eight additional affected relatives. In the 11 ADPKD- IFT140 patients, the renal phenotype was characterized by mild and late-onset PKD, with large renal cysts and limited kidney insufficiency. Extrarenal manifestations, including liver cysts, were rarely seen., Conclusion: Our data suggest the monoallelic pathogenic IFT140 variants are the third most common cause of the ADPKD-spectrum phenotype in Italy, usually associated with a mild and atypical renal cystic disease., Competing Interests: F.A. has received consulting fees from GSK, Vifor Pharma, AstraZeneca and Novartis. All other authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare inherited disorder characterized by progressive loss of kidney function, nonsignificant urinalysis and tubulointerstitial fibrosis. ADTKD progresses to end stage renal disease (ESRD) in adulthood. The classification of ADTKD is an evolving concept and the agreement is now that, due to the overlap in terms of phenotype characteristics, this should be based on the involved gene. The umbrella term ADTKD therefore includes different conditions as follows: ADTKD- UMOD , ADKTD- MUC1 , ADTKD-REN, and ADTK- HNF1B, with ADTKD- SEC61A1 and ADTKD- DNAJB11 as a further rare and atypical diagnosis recently described. The employment of next-generation sequencing (NGS) as a diagnostic tool in patients with familial kidney disease has improved the diagnostic accuracy in this field with ADTKD now being considered the third genetic cause of renal disease worldwide after autosomal dominant polycystic kidney disease (ADPKD) and Alport syndrome. On average, the disease pathogenesis is similar across the different subtypes, With the exception of HNF1B , the different mutated genes give rise to misfolded proteins leading to cellular stress and cytotoxicity. Research is now focused in better defining the underlying mechanism of fibrosis to guide therapeutic interventions. The aim of this review is to discuss how the knowledge of ADTKD has evolved in the last decades, with emphasis on the clinical features, molecular diagnosis, and pathogenic aspects of the different diseases included under the ADTKD term., (© 2022 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary nephropathy and is the fourth most common cause for end-stage renal disease in Europe. ADPKD is a systemic disease; besides the typical renal involvement, characterized by progressive cyst expansion leading to massive enlargement and distortion of the kidney architecture and, ultimately, to end-stage renal disease, multiple extrarenal manifestations can be observed included cysts in other organs, diverticulosis, cardiac valvulopathies, abdominal and inguinal hernias, vascular anomalies. The rupture of an intracranial aneurysm is one of the most serious complications in ADPKD patients. Aim of this review is to provide useful indications for the clinician to define the risk of intracranial aneurysms in ADPKD population, to identify screening criteria (which patients to screen, how often and with which diagnostic methods), to estimate the risk of rupture of intracranial aneurysms, which may require intervention., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

The SARS-CoV-2 epidemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience of four dialysis centers of the Brescia Renal COVID Task Force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis, whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70), and dyspnea at presentation were associated with the risk of developing ARDS, whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The analysis of the national and international literature reveals a prevalence of around 20% of work-related musculoskeletal disorders in construction workers over 40 years of age. The chronic-degenerative disease in the muscular-skeletal system is important not only for the number of reported cases, but also for the seriousness of the symptoms, which are one of the main causes of evaluations of limited work-suability and unfitness for work. The aim of this study is to improve the quality of the diagnosis of occupational musculoskeletal illnesses and to ensure that the occupational physicians identify such disease, as prescribed by the Italian legislation about safety and health in workplaces. The research involved 57 construction companies located in the Bergamo's province, which employ, in aggregate, 833 workers. A sample of 479 workers, 40, or more, years old (403 Italians and 76 foreigners) was analysed. It was found out that 152 workers had some musculoskeletal disorders but only for 5 of them an occupational disease was already reported. It was necessary to ask the occupational physician for further clinical investigation for 60 employees, which revealed 29 new musculoskeletal occupational diseases in 19 workers. At the end of the study a total of 34 musculoskeletal occupational diseases were diagnosed in 22 workers: it was 4, 6% of the total sample investigated (n. 479) and 14% of those who already had problems (no 152). The results confirm the under-reporting of occupational musculoskeletal diseases in construction workers. The active research is a useful tool for the purposes of verifying the level of health surveillance carried out by occupational physicians. In fact the study highlighted that physicians seem not to be inclined to require additional clinical investigations and not always report occupational diseases.

Morphological changes of dermal blood and lymphatic microcirculation in skin biopsies from patients affected by Chronic Venous Insufficiency (CVI) associated with stasis dermatitis of the lower limbs, are reported here. Blood vessels are characterized by an occluded lumen, thickening and reduplication of the basement membrane. The structural changes in dermal lymphatic vessels are: (i) collapsed lumen of lymphatics located in the papillar dermis; (ii) numerous and complex interdigitations between contiguous endothelial cells and lack of open junctions; (iii) derangement of the anchoring filaments that normally pull the lymphatic lumen open. The connective matrix is characterized by fibrosis with formation of dense bundles of collagen and elastic fibers. These results suggest that the dermal lymphatic and blood microcirculation in CVI are connected to a reduced fluid exchange capacity because of the structural changes occurred in the vascular and lymphatic wall and in the surrounding connective tissue.

A careful study of the principal multidrug regimes wil reveal in each case the criteria upon which the drug association was based. In this paper the authors emphasize the importance of correlating the parameter, point of attack of the drug, with the parameter, metabolism of the malignant cell, the latter being differentiated into different functions according to thermodynamic criteria and to the particular organization of enzyme systems in the cells. Thus a multidrug association will be the more rational, the greater the number of parameters taken into consideration in its engineering; in these terms the authors outline a method of drug association affording more and more complex combinations and also the replacement of one or more component drugs in the case of resistance phenomena.

In view of the necessity for patients under periodical dialysis to preserve in operating condition the artero-venous fistulas performed on them, so that the application of the dialytic processes is extended as much as possible, particular technical suggestions are put forward, also taking into account the requirements of immediate dialysis for acute uremia and endeavouring to recover any artery and vein that may be used for external by-passes.

A theoretical physical study of the variations of the distribution of the flow in a branched system of vessels is presented. The possible applications are prospected.

The stresses and deformations which the blood vessels are subjected in relation to variations of their tonus and their geometrical characteristics are considered. The problema is defined from the physical standpoint.