Case report no. 9.Recurrence of amyloid in a kidney allograft

Eva HonsováInstitute for Clinical and Experimental MedicinePrague, Czech Republic

Clinical history• A 55-year-old man was admitted to the hospital for severe

hypertension in 1989.• He was well until half a year before when slowly

progressing peripheral edema appeared.• He didn’t consult his practitioner until he began to suffer

from severe headaches with nausea, and blurred vision.• 210/130mmHg• proteinuria 6g/day, S-Cr level was 296umol/l (3,3mg/dl)• there was a 10 times higher level of antibodies against

streptolysin O (ASLO). • A renal biopsy was performed with clinical diagnosis of

postinfectious glomerulonephritis.

Native kidney biopsy sample (from 1989)IF: Igs negative, C3 negat., kappa, lambda: negat.

PAS staining Congo red

Dg: Amyloidosis of an uncertain type.

• Extensive searching for some disease associated with amyloidosis

• 2 nodules in the liver; biopsy unsuccessful• No evidence of inflammatory disease• No evidence of plasma cell dyscrasia• No other disease in addition to DM type II• Half a year later: viral respiratory illness; kidney

function rapidly declined and hemodialysis was begun.

• Family medical historyBoth parents dead (mother: 40, abdominal tumor; father: 77, DM, IHD; sister: 7, car accident)2 children, a son and a daughter: healthyNo evidence of kidney disease

• Because of uncertain biological potential of liver lesions, he was not included in the waiting list.

• Liver masses were stable for 3 years. • Patient´s data were reevaluated, 6 years after

kidney failure he underwent kidney transplantation.

• Kidney graft had excellent function for the following 15 years.

• No kidney graft biopsy was performed.• Recently, proteinuria was revealed and a

kidney graft biopsy was performed with clinical suspicion of diabetic nephropathy and chronic rejection.

Graft biopsy sampleIF: C4d negative; Igs negative; C3,C1q: negative; kappa: negative; lambda: weakly positive, AA:neg.

Genetic studies were performed and mutation in the fibrinogen gene was confirmed (Glu526Val)

G Graft biopsy sample, IF & IH detection fibrinogen A r

Skin biopsy sample; subsequent IF and IH for fibrinogenA

Follow-up• No change in immunosuppressive treatment• S-Cr 178μmol/l (2.01mg/dl)• PU 3.6g/day• DM under control

• Recently, genetic analysis for his 2 children was offered

Diagnosis of the type of amyloidosis

The most common types: AA+ALAA (commercial antibodies)AL (low reactivity of commercial Abs in paraffin sections)Hereditary amyloidoses: more frequently recognized,

are gaining in clinical importance. Autosomal dominant, variable penetrance, family history is lacking, clinical manifestation at older ages, therefore the correct diagnosis is challenging

Each type requires different therapy, dg must be based on identification of the protein

Hereditary fibrinogen A amyloidosis• Mutation in Fibrinogen Aα-chain gene was first

described by Benson et al. in 1993• most frequent hereditary amyloidosis in the UK and

also in Europe• All cases: renal biopsy samples with massive and

exclusively glomerular amyloid deposits• Median age of presentation: 55years• Fibrinogen: produced exclusively by the liver• Kidney transplantation alone associated with rapid

recurrence of amyloid• Liver or combined liver and kidney transplantation

Fascinating story of amyloidosis

• Not all of patients with „preconditions“ suffer from amyloidosis

• Genetic factors, different types of degradation• Per Westermark: different point of view• Comparison with prion diseases: change in the

protein structure• In experiments, amyloid enhancing factor• Amyloid fibrils were identified as the basis of AEF• Prion diseases are transmissible by food

Is amyloidosis transmissible? • Yes, very probably • Westermark GT, Westermark P. Serum amyloid A and protein AA:

molecular mechanisms of a transmissible amyloidosis. FEBS Lett. 2009;583:2685-2690.

• AA amyloidosis is transmissible in several animal experimental models • AA amyloid can occur in human food(ducks, geese: pate de foie gras)• AA amyloidosis is transmissible by blood monocytes• Will we change the management of patients at risk of amyloidosis?

ESP Congress, Prague 2012