HDCN Ask the Professor:

Suspected Renal Amyloidosis

This case is a diagnostic dilemma for me: A 55-year old male was referred with hepatomegaly and elevated alkaline phosphatase and gamma GT. Liver biopsy showed AL amyloidosis. The patient was noted to have proteinuria. Serum creatinine was 1.2 mg%, serum albumin 3.5 g%, 24-hour urinary protein excretion 7 grams, and creatinine clearance 70 ml/minute. Renal biopsy was not done but a diagnosis of systemic amyloidosis affecting liver and kidney was made.

Serum and urine electrophoresis were negative, and marrow aspirate was normal. Skeletal survey was negative.

After six months' follow-up the patient's condition is unchanged. The proteinuria has not responded to ACE inhibition.

Questions:
1. Is renal biospy necessary, or is the diagnosis obvious?
2. Would anyone treat with melphalan and prednisone or anything else?
3. What is the prognosis for a patient following such an apparently indolent course? Are any other investigations suggested?

Peter G. Blake, MB, FRCPC (London, Ontario, Canada)


Response by Dr. Robert A. Kyle, M.D.
Professor of Medicine and Laboratory Medicine
Mayo Clinic School of Medicine, Rochester, Minn.

I agree that the diagnosis is most likely AL amyloidosis, but it is unusual to have no monoclonal protein in the serum and urine and no monoclonal populations of plasma cells in the bone marrow. Were immunohistochemical stains of the liver biopsy done? In my experience, 90% of patients will have a monocalonal protein in the serum or urine or a monoclonal population of plasma cells in the bone marrow. If an M-protein and monoclonal plasma cells are absent, immunohistochemical stains must be done on the liver biopsy in order to ascertain the type of amyloid.

It is most likely that the patient has amyloid involving the kidney, but one cannot be certain. The fact that the patient's proteinuria and creatinine clearance are stable is unusual for AL amyloidosis. Does the patient have any other features of amyloidosis such as purpura, macroglossia, peripheral neuropathy, orthostatic hypotension, carpal tunnel symptoms, weight loss, or an abnormal echocardiogram?

I am inclined to perform a renal biopsy in this patient because of the atypical features. I would also perform an echocardiogram looking for abnormalities in diastolic function.

I would not treat the patient until the diagnosis of AL amyloidosis is established. The standard treatment would be melphalan and prednisone, but a peripheral stem cell procedure or 4'-iodo-4'-deoxydoxorubicin, when it becomes available, would be other therapeutic considerations.

(March, 1996)

An alternative route to the diagnosis of systemic amyloidosis would be to perform a radio-iodine labelled serum amyloid P (SAP) component scan. The SAP binds to the amyloid fibrils and is a quantitative marker of amyloid load and distribution. The SAP scan has a very high specificity and sensitivity. In addition, a trephine biopsy of the bone marrow should be performed - we have seen a case of myeloma where the bone marrow contained, in effect, focal microplasmacytomas which were missed on several bone marrow aspirates but became apparent on trephine.
Dr Andrew Allen
London, UK-Wednesday, April 10, 1996 at 13:33:18 (CDT)

1. I would do a rectal biopsy to look for confirmation of Amyloidosis. In this I can avoid a renal biopsy. 2. It is imperative that a diagnosis should be established as soon as possible since treatment with adequate amounts of colchicine is supposed to help in preventing the advance of the disease even at this late stage. 3. If I cannot get a meaningful rectal biopsy I would go for renal biopsy.
H Eliahou (eliahou@ccsg.tau.ac.il)
Ramat Gan, Israel-Friday, April 19, 1996 at 04:13:27 (CDT)