Those with End-stage kidney disease face many problems when they don’t go for transplantation in time due to which they go for a long duration hemodialysis in which some harmful substances will build up. This has confirmation from 1970s research studies of carpal tunnel syndrome patients undergoing hemodialysis. The first reason for this build up was thought to be from the pressure of the vein due to dialysis fistulas. Later, few studies revealed the exact reason behind the amyloid deposits in synovium of the patients on hemodialysis, which has beta-2 microglobulin composition. This deposition has given this disease a name ” Dialysis-related beta-2m amyloidosis”. This also affects organs other than kidneys. 

In USA, the cases of dialysis-related beta-2m amyloidosis are not clear. Past studies of patients who are on hemodilaysis for more than 15 years showed a rate of prevalence of 95%. In Europe, patients who are on hemodialysis for 2 or 4 years and more than 13 years showed a rate of 20%. But here the reason was not clear. Previously, studies focused only on HD-related amyloidosis. Later, high-flux dialyzers came into play. A few risk factors taken into consideration are age, dialysis membranes that are incompatible, and dialysis duration, which is longer. These are the same risk factors for peritoneal dialysis. These studies showed a decrease in DRA cases with compatible dialysis membranes. Surgery will be the last option if any other options doesn’t work. 

At first, researchers thought that these deposits were formed due to native molecule splitting. Later, they found that beta-2 microglobulin was the reason behind the amyloid deposits. In this case, the deposits were formed by folding more amino acids into beta-sheets. Hence, the name beta-2 microglobulin. Because of the improper functioning of the kidneys and their decreased filtering capacity, these deposit levels of B2M were 25 and 34 mg/L. Old dialysis procedures only remove a little B2M accumulation. But high-flux dialyzers work more efficiently in clearing B2M accumulation. Lab tests confirmed high levels of B2M accumulation is due to amyloid formation which led to damage to the tissues by glycation products resulting in the inflammation which involves fibroblasts, monocytes, and matrix enzymes. 

Amyloid deposits are formed through polymerization in various tissues by the B2M appearance of monomers circulating which are found on surfaces of the cells and in body fluids. Most individuals with CKD show a raised levels of B2M that lead to amyloidosis. The fact which is interesting here is dialysis is generally removes waste from the body, but it makes B2M to accumulate and build up due to the incompatible membranes of dialysis (outdated method). High-flux dialyzers came into picture to address this accumulation and effective clearance of B2M. A few risk factors taken into consideration are age, dialysis membranes that are incompatible, and dialysis duration, which is longer. These are the same risk factors for peritoneal dialysis. There are few other etiologies which include uremia which is prolonged, glycation end products which are advanced, and inflammation which leads to B2M accumulation. 

The issues faced or experienced by CKD patients undergoing dialysis for longer duration are associated with certain risk factors such as age, incompatible dialysis membrane, and their duration on dialysis. These patients experience musculoskeletal issues as well. Kidney transplantation can stop this disease which only helps partially to reverse the damage occurred. The accumulation of B2M led to complications such as pulmonary hypertension, heart failure, and gut bleeding. Other studies from Japan showed that these deposits can lead to high-risk carpal tunnel syndrome in CKD patients who are on dialysis for more than 10 years duration. This complication increases more in patients with dialysis duration of more than 20 years. 

The symptoms exhibited by CKD patients on dialysis for more duration are worst from feeling weak and tired to experiencing musculoskeletal issues such as pain in the joints. The symptoms which got worse are accumulation of amyloid deposits in various tissues. Tingling, Weakness in hands and wrists are the symptoms of carpal tunnel syndrome. These are the people who struggle with tasks they handle regularly and also with gripping issues. Overtime, these can lead to shoulder pain, triggers in the finger, skin lumps, and darker patches. Examination of patients is concluded by their history of HD duration and surgeries if any. 

The physical examination is done by examining the hands of patients for thenar muscle wasting, reduced feeling in the median nerve areas, and positive Phalen’s or Tinel’s tests, linked to carpal tunnel syndrome. Triggering in the fingers is associated with thickening or bumps in the flexor tendons. The shoulder examination is done for tenderness around any musculoskeletal joints which includes acromioclavicular joints and overhead arm motion which is limited. The skin examination is done for palpable nodules under the skin, plaques, and darker patches. Other conditions associated are heart murmurs, gut bleeding, and any neurological deficits. 

DRA patients exhibit raised levels of B2M which is the reason behind the symptoms. This can occur overtime with risk factors such as old-age, incompatible dialysis membranes, and duration of dialysis. These symptoms together lead to carpal tunnel syndrome or other digestive issues. The symptoms of heart failure appear fast in some patients with long duration of dialysis. This will help us to diagnose fast and treat the disease and avoid further complications that occur if it is not addressed. 

DRA can be treated in two ways. First is to address or managing musculoskeletal issues and second by removing amyloid deposits and preventing new lesions. In most patients, pain killers are prescribed to treat existing joint pains. Kidney transplantation in patients gives hope in clearing B2M levels effectively and gives relief from stiffness and shoulder pain. High-flux dialyzers and hemodiafiltration are the methods used to remove more B2M accumulation. The antibiotics used to treat metabolic acidosis provides some help. The use of Lixelle column in HD helps to absorb and remove B2M accumulation which lead to improved quality of life with fewer symptoms in DRA patients. Conservative therapies which provide help are physiotherapy, carpal tunnel release, NSAIDs, and joint replacement surgeries. 

Nephrology

DRA patients require lifestyle modifications which includes good health, early management of symptoms, limited exercise is preferred. These lifestyle modifications improve the movement, gives muscle strength, and overall health. Strenuous activities that should be avoided to avoid pain and fractures. In CKD, a low potassium and low phosphorous advised. Limit all processed foods, high potassium fruits, vegetables, and dairy. Staying in hydration is good for kidneys to function properly. No smoking and no alcohol to avoid complications. These all will lead to overall quality of life. 

Nephrology

ibuprofen: It is used in the treatment of pain from DRA. This NSAID can harm kidneys and cause bleeding issues internally, especially in kidney patients. Monitoring is required in patients with DRA.  

Sulindac:  It reduces swelling in the joints and helps to ease the DRA pain.   

Nephrology

Capsaicin topical: This cream when applied eases pain in DRA by numbing nerves which reduces discomfort. Its actions are different for different persons. 

Nephrology

Triamcinolone: It is a corticosteroid that reduces swelling and pain in patients with DRA. It is injected into joints for targeted relief. Its actions are different in various patients. 

Prednisone: It helps to reduce inflammation and discomfort due to joint aches in patients with DRA. It reduces immune response and inflammatory substances. 

Prednisolone:  It helps to reduce inflammation, joint pains, and swelling. It is taken in small doses just like prednisone. 

10% hydrocortisone cream: It is used in the management of issues in DRA such as skin irritation, itching, or inflammation due to amyloid deposits. It is applied directly to the affected areas which reduces discomfort and gives improvement in the state of the skin. 

Nephrology

Doxycycline:  It helps in fighting the DRA disease by inhibiting fibril formation which are the amyloid deposits which gives trouble in movement. It may relieve symptoms which eases movement. 

Nephrology

DRA patients are required to eat healthy foods. They need to have a balanced diet when they are on dialysis which includes low potassium and low phosphorous with right proteins. They need to stay on hydration always. There could a variation or slight modification in the diet because of joint or bone issues resulting from DRA. Proper nutrition is the goal during dialysis.

Nephrology

To restore the function and for giving relief, DRA requires surgical methods which include carpal tunnel release, spinal stabilization, flexor tenosynovectomy, and joint replacement. But these procedures fail in patients with DRA. The FDA-approved Lixelle B2M apheresis column is the promising option in effectively clearing B2M accumulation in HD sessions. Kidney transplantation is the definitive approach in reducing the levels of B2M and to stop the progression of the disease. DRA can be prevented by hemodiafiltration, High-flux dialyzers, ultrapure dialysate preparations, and adsorbent columns. Laser therapy helps in preventing amyloid fibril deposition and to destroy amyloid deposits which are preformed. Comprehensive care is provided by collaborating with various specialists which includes surgery, rheumatology, nephrology departments with transplantation consultants. 

Nephrology

 DRA is treated in multiple ways. First, musculoskeletal issues are addressed preventing B2M accumulation. Surgeries like joint replacement or carpal tunnel release which provide some relief. The FDA approved Lixelle B2M apheresis column offers some promise which aims to clear B2M accumulation. Kidney transplantation is the better option in giving relief to bone issues and clearing B2M accumulation by lowering the levels and stopping the progression of the disease. Lifestyle modifications, corticosteroids, NSAIDs, and other nutritional diet plans help to manage the symptoms and improve the quality of life of the patients. DRA is treated by collaborating with various specialists providing comprehensive care. High-flux dialyzers and ultrapure dialysate preparations are the preventive measures which can help to prevent DRA.