Gregorini G et al. (2005) Renal apolipoprotein A-I amyloidosis: a rare and usually ignored cause of hereditary tubulointerstitial nephritis. J Am Soc Nephrol 16: 3680–3686

Mutations in apolipoprotein A-I (apoA-I) result in deposition of amyloid fibrils, predominantly in the liver, kidney and heart, and cause a rare, late-onset, autosomal dominant form of amyloidosis. In a paper published in the Journal of the American Society of Nephrology, Gregorini et al. add to their previous data regarding renal involvement in patients with hereditary apoA-I amyloidosis associated with a Leu75→Pro heterozygous mutation.

The authors analyzed 13 members of five kindreds native to Northern Italy, and showed this form of amyloidosis to manifest as a tubulointerstitial disorder with renal involvement that varied widely in severity but was in most cases slowly progressive. Age at disease onset ranged from 42 to 68 years. The phenotype was relatively mild compared with other forms of amyloidosis, and characterized by a marked prominence of liver and kidney disease. Unlike most other forms of systemic amyloidosis, which show predominantly glomerular and vascular deposits, amyloid deposition in this apoA-I variant was only in nonglomerular regions and was limited to the renal medulla.

Renal disease would therefore appear to be substantially different in systemic apoA-I amyloidosis than in typical glomerulopathic systemic amyloidoses. The nature of renal amyloid deposition in the apoA-I variant makes differentiation from other forms of hereditary tubulointerstitial nephritis with prevalent medullary involvement difficult, and the correct diagnosis could easily be missed—especially if only cortical tissue is analyzed. The authors urge clinicians to pay particular attention to a diagnosis of apoA-I amyloidosis in patients presenting with familial tubulointerstitial nephritis associated with liver disease.