title: Renal apolipoprotein A-I amyloidosis: a rare and usually ignored cause of hereditary tubulointerstitial nephritis.
abstract: Apolipoprotein A-I amyloidosis is a rare, late-onset, autosomal dominant condition characterized by systemic deposition of amyloid in tissues, the major clinical problems being related to renal, hepatic, and cardiac involvement. Described is the clinical and histologic picture of renal involvement as a result of apolipoprotein A-I amyloidosis in five families of Italian ancestry. In all of the affected family members, the disease was caused by the Leu75Pro heterozygous mutation in exon 4 of apolipoprotein A-I gene, as demonstrated by direct sequencing and RFLP analysis. Immunohistochemistry confirmed that amyloid deposits were specifically stained with an anti-apolipoprotein A-I antibody. The clinical phenotype was mainly characterized by a variable combination of kidney and liver disturbance. The occurrence of renal involvement seemed to be almost universal, although its severity varied greatly ranging from subclinical organ damage to overt, slowly progressive renal dysfunction. The renal presentation was consistent with a tubulointerstitial disease, as suggested by the findings of defective urine-concentrating capacity, moderate polyuria, negative urinalysis, and mild tubular proteinuria. Histology confirmed tubulointerstitial nephritis. Surprising, amyloid was restricted to nonglomerular regions and limited to the renal medulla. This location of apolipoprotein A-I amyloid differs sharply from other systemic amyloidoses that are mainly characterized by glomerular and vascular deposits. The tubulointerstitial nephritis as a result of hereditary apolipoprotein A-I amyloidosis is a rare disease and a challenging diagnosis to recognize. Patients who present with familial tubulointerstitial nephritis associated with liver disease require a high index of suspicion for apolipoprotein A-I amyloidosis.
authors.affiliation: Division of Nephrology, Spedali Civili, Brescia, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Gregorini
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.forename: Regina
authors.initials: R
authors.lastname: Tardanico
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Battista Fabio
authors.initials: BF
authors.lastname: Viola
authors.forename: Mariano
authors.initials: M
authors.lastname: Capistrano
authors.forename: Simona
authors.initials: S
authors.lastname: Donadei
authors.forename: Luciano
authors.initials: L
authors.lastname: Biasi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Scalvini
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D028226:Amyloidosis, Familial / Q000453:epidemiology / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000235:genetics*; D001707:Biopsy, Needle; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009394:Nephritis, Hereditary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009395:Nephritis, Interstitial / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011379:Prognosis; D035583:Rare Diseases; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D016632:Apolipoprotein A-I