PMID- 38514012 OWN - NLM STAT- Publisher LR - 20240321 IS - 1523-6838 (Electronic) IS - 0272-6386 (Linking) DP - 2024 Mar 19 TI - Clinical Significance of the Cystic Phenotype in Alport Syndrome. LID - S0272-6386(24)00681-4 [pii] LID - 10.1053/j.ajkd.2024.02.005 [doi] AB - 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. EXPOSURES: Cystic kidney phenotype evaluated by ultrasonography and defined as the presence of >/=3 cysts in each kidney. Demographic characteristics and eGFR at disease onset. OUTCOMES: Cystic kidney phenotype in the AS and IgAN cohorts. Time to 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 genetic diagnosis. Autosomal dominant AS was prevalent, accounting for 68% of patients with 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 (ADPKD). The prevalence of cystic kidney phenotype was significantly higher in patients with AS when compared to comparison group of patients with IgAN (42% vs 19%; p=0.002). Patients with cystic kidney phenotype were older and had more marked reductions 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. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Zeni, Letizia AU - Zeni L AD - Division of Nephrology and Dialysis, ASST-Spedali Civili of Brescia, Brescia, Italy. FAU - Mescia, Federica AU - Mescia F AD - Division of Nephrology and Dialysis, ASST-Spedali Civili of Brescia, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. FAU - Toso, Diego AU - Toso D AD - Division of Nephrology and Dialysis, ASST-Spedali Civili of Brescia, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. FAU - Dordoni, Chiara AU - Dordoni C AD - Clinical Genetics Unit, Department of Obstetrics and Gynaecology, ASST-Spedali Civili Brescia, Italy. FAU - Mazza, Cinzia AU - Mazza C AD - Medical Genetics Laboratory, ASST-Spedali Civili, Brescia, Italy. FAU - Savoldi, Gianfranco AU - Savoldi G AD - Medical Genetics Laboratory, ASST-Spedali Civili, Brescia, Italy. FAU - Econimo, Laura AU - Econimo L AD - Division of Nephrology and Dialysis, ASST-Spedali Civili of Brescia, Brescia, Italy. FAU - Cortinovis, Roberta AU - Cortinovis R AD - Division of Nephrology and Dialysis, ASST-Spedali Civili of Brescia, Brescia, Italy. FAU - Fisogni, Simona AU - Fisogni S AD - Section of Pathology, Department of Molecular and Translational Medicine, ASST-Spedali Civili, University of Brescia, Brescia, Italy. FAU - Alberici, Federico AU - Alberici F AD - Division of Nephrology and Dialysis, ASST-Spedali Civili of Brescia, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. FAU - Scolari, Francesco AU - Scolari F AD - Division of Nephrology and Dialysis, ASST-Spedali Civili of Brescia, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. FAU - Izzi, Claudia AU - Izzi C AD - Clinical Genetics Unit, Department of Obstetrics and Gynaecology, ASST-Spedali Civili Brescia, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address: claudia.izzi@unibs.it. LA - eng PT - Journal Article DEP - 20240319 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 SB - IM OTO - NOTNLM OT - Alport Syndrome OT - Autosomal dominant Alport Syndrome OT - COL4A3 OT - COL4A4 OT - COL4A5 variants OT - Cystic kidney disease OT - Genetic kidney disease OT - IgA Nephropathy and kidney cysts OT - Kidney cysts EDAT- 2024/03/22 00:44 MHDA- 2024/03/22 00:44 CRDT- 2024/03/21 20:31 PHST- 2023/09/21 00:00 [received] PHST- 2024/01/16 00:00 [revised] PHST- 2024/02/02 00:00 [accepted] PHST- 2024/03/22 00:44 [medline] PHST- 2024/03/22 00:44 [pubmed] PHST- 2024/03/21 20:31 [entrez] AID - S0272-6386(24)00681-4 [pii] AID - 10.1053/j.ajkd.2024.02.005 [doi] PST - aheadofprint SO - Am J Kidney Dis. 2024 Mar 19:S0272-6386(24)00681-4. doi: 10.1053/j.ajkd.2024.02.005.