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1.
Am J Kidney Dis ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38514012

RESUMO

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.

2.
Clin Kidney J ; 17(2): sfae026, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38404363

RESUMO

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.

3.
Kidney Int Rep ; 7(11): 2332-2344, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36531871

RESUMO

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.

5.
G Ital Nefrol ; 38(5)2021 Oct 26.
Artigo em Italiano | MEDLINE | ID: mdl-34713642

RESUMO

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.


Assuntos
Aneurisma Intracraniano , Falência Renal Crônica , Rim Policístico Autossômico Dominante , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/terapia , Rim , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/terapia
6.
Kidney Int ; 98(1): 20-26, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32437768

RESUMO

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.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Falência Renal Crônica/complicações , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Síndrome do Desconforto Respiratório/virologia , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/uso terapêutico , Itália/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Diálise Renal , Síndrome do Desconforto Respiratório/epidemiologia , Estudos Retrospectivos
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