Beta 2-microglobulin amyloidosis is a common condition affecting patients on long-term hemodialysis Carpal tunnel syndrome is the most common mononeuropathy in dialysis patients caused by compression of the median nerve at the level of wrist where it passes via narrowed carpal tunnel.

Case report

A 75 year old female, diabetic and hypertensive for more than 10 years, on irregular treatment presented to us in End stage renal failure stage (ESRD). Started on maintenance HD (low-flux dialyzer) thrice weekly through AV fistula, since November 2017. After being on dialysis for past 4 years, she recently complained of small joint pain on both upper and lower limbs and numbness of hands.

For which she consulted a neurologist. Nerve conduction study done shows bilateral median nerve compression suggestive of carpal tunnel syndrome. X-ray of hand showed arthropathy changes with bone cycts (Image). Since she is on long term dialysis beta2 microglobulin protein was checked and found to be elevated (23.4 mg/L). Hence the diagnosis of Carpal tunnel syndrome secondary to Beta2 microglobulin amyloidosis was made.

(Image) X-ray of the hand showing bone cysts and narrowing of joint spaces.

Discussion

Excess small proteins are usually filtered by normally functioning kidneys. In chronic kidney disease, patients on hemodialysis, one type of small protein called beta 2-microglobulin level rises in blood. When this happens, beta 2-microglobulin molecules may join together, like the links of a chain, forming a few very large molecules from many smaller molecules. These large molecules can form deposits and leads damage the surrounding tissues and cause great discomfort. This is termed as dialysis-related amyloidosis (DRA).

Amyloidosis is characterized by the extracellular deposition of insoluble fibrillar proteins collectively termed amyloid, a starch like substance. Clinical manifestations usually never appears before 5 years of Hemodialysis. Beta 2-microglobulin amyloid is largely confined to osteoarticular sites, which differentiates from other amyloid types. Patients usually presents with symptoms of CTS, shoulder pain, and flexor tenosynovitis in the hands, which forms a triad. Visceral deposits can occur after 10 years, but mostly asymptomatic. The diagnosis of beta 2-microglobulin amyloidosis is generally made by its clinical appearance on tissue or bone biopsy. The normal level of serum  beta 2-microglobulin is 1.5–3 mg/l. Beta 2-microglobulin levels correlate with elevated serum creatinine levels and are inversely related to the GFR.

DRA is common in older adults, who have been on hemodialysis for more than 5 years. The major reason for increased beta2-m level was use of low-flux dialyzers. High flux dialyzers are made of large pores, which has  enough space to allow the passage of large molecules like beta2 microglobulin (molecular weight 11,800 d).

Treatment and Prevention

USG shows Aβ2Mamyloidosis as thickening of the joint capsules of the hip and knee, biceps tendons, and rotator cuffs, as well as the presence of echogenic structures between muscle groups and joint effusions. On radiologic examination, affected joints may present with single or multiple juxtaarticular, “cystic” bone radiolucencies. Treatment for Aβ2M amyloidosis is symptomatic. Medical management includes NSAIDs and physiotherapy. Surgical treatment like carpal tunnel decompression, endoscopic coracoacromial ligament release, and bone stabilization in areas of cystic destruction. By using high-flux hemodiafiltration, CTS risk can be reduced by 40 to 50%. A drastic reduction in the prevalence of carpal tunnel syndrome is seen in patients dialyzed with ultrapure dialysate. In another study, an 80% reduction of amyloid signs in a chronic HD population appeared to relate to dialysate factors like microbiologic purity and bicarbonate buffer use.

In our patient, after changing to high flux dialyzer with 5008S dialysis machine, slowly symptoms settled down and improved symptomatically. Beta 2 microglobulin protein levels checked were also decreased. Currently she is on thrice weekly maintenance HD with High flux dialyzer.

References:

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Dr.S.Vishnu Shankar
First Year DrNB (Nephro) Resident
Department of Nephrology

Dr Pratheeba
First Year DrNB (Nephro) Resident
Department of Nephrology