title: Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A-I amyloidosis.
abstract: Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.
authors.affiliation: Division of Nephrology, Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Gregorini
authors.affiliation: 1] Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy [2] Prenatal Diagnosis Unit, Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.affiliation: Department of Medicine and Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.affiliation: Amyloidosis Research and Treatment Centre, Biotechnology Research Laboratories, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.affiliation: Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Dallera
authors.affiliation: Division of Internal Medicine, Montichiari Hospital, Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Del Barba
authors.affiliation: Division of Nephrology, Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Negrinelli
authors.affiliation: Department of Pathology, Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Regina
authors.initials: R
authors.lastname: Tardanico
authors.affiliation: Division of Cardiology, Spedali Civili, University of Brescia, Brescia, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Nardi
authors.affiliation: Division of Infectious and Tropical Diseases, Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Biasi
authors.affiliation: Division of Internal Medicine, Montichiari Hospital, Brescia, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Scalvini
authors.affiliation: 1] Amyloidosis Research and Treatment Centre, Biotechnology Research Laboratories, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.affiliation: Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D028226:Amyloidosis, Familial / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000209:etiology; D008107:Liver Diseases / Q000209:etiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D019683:Penetrance; D012189:Retrospective Studies; D013733:Testicular Diseases / Q000209:etiology / Q000473:pathology
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D003404:Creatinine; D000469:Alkaline Phosphatase