Bence-Jones proteinuria is the presence of light-chain renal toxic paraproteins, Bence-Jones proteins, in the urine. These functionless light chain proteins represent fragments of antibodies produced by B lymphocytes. Their increased occurrence often indicates malignant proliferation of B lymphocytes.
What is Bence-Jones proteinuria?
In Bence-Jones proteinuria, so-called Bence-Jones proteins are excreted in the urine. Bence-Jones proteins represent light-chain proteins derived from antibodies. They are formed especially in cancers of the hematopoietic system. Their presence in urine can thus indicate a malignant proliferation of lymphocytes. However, increased Bence-Jones proteins can also be formed in benign proliferation of lymphocytes during an infection. The Bence Jones proteins were first described in 1848 by the English physician Henry Bence Jones. He also recognized a connection between the occurrence of these proteins and multiple myeloma. Thus, Bence Jones proteinuria is even considered to be unambiguously characteristic for this disease. Bence-Jones proteinuria is not a disease in its own right, but a symptom of lymphoma, multiple myeloma, Waldenström’s disease and transient increased lymphocyte production. However, the Bence-Jones proteins themselves are toxic to the kidneys and can lead to renal insufficiency when exposed chronically. Renal toxicity results from the protein’s ability to form deposits in the glomerular capillaries or distal renal tubules. This results in long-term renal damage and renal failure.
Causes
Causes of Bence-Jones proteinuria include multiple myeloma, Waldenström’s disease, various lymphomas, transient increased formation of immunoglobulins during infections, or monoclonal gammopathy of uncertain significance (MGUS). Multiple myeloma is a cancer of the hematopoietic system. In this case, there is increased formation of monoclonal B lymphocytes in the bone marrow. As a result, monoclonal antibodies and light chain proteins (parts of the immunoglobulins) are formed. The light chain proteins or Bence-Jones proteins are functionless and are excreted in the urine. Multiple myeloma, on the other hand, is not a uniform disease. It always starts from a single degenerated cell which, as a result of its uninhibited proliferation, displaces the other cells of the hematopoietic system. Other lymphomas and Waldenström’s disease can also lead to the formation of Bence-Jones proteins. These diseases also involve malignant proliferation of lymphocytes. Waldenström’s disease is similar to multiple myeloma. However, the course of the disease is much slower. However, Bence-Jones proteinuria may also occur in monoclonal gammopathy of uncertain significance (MGUS). MGUS is a precursor to the above-mentioned cancers in a few cases. The term gammopathy refers to the gamma fraction in the detection of Bence-Jones proteins in serum protein electrophoresis. However, transient gammopathy can also occur as a result of enhanced immune responses in infectious diseases.
Symptoms, complaints, and signs
The main symptom of Bence-Jones proteinuria is the increased presence of light-chain proteins in the urine. The other symptoms are determined partly by the underlying disease and partly by the subsequent damage to the kidneys from the influence of the light chains. In the case of a simple monoclonal gammopathy of unclear significance, it is also possible that no other symptoms occur. In multiple myeloma, bone pain, loss of bone substance, shoulder pain, back pain, fatigue, loss of performance, susceptibility to infection, as well as fever, weight loss, and night sweats occur. Similar complaints are also observed in the other lymphomas and in Waldenström’s disease. In Waldenström’s disease, often no symptoms appear at all for years. Damage to the kidneys in advanced stages of the disease, if left untreated, can lead to urinary toxicity with nausea, vomiting, bleeding tendencies, and impaired consciousness, even coma.
Diagnosis and course
Bence Jones proteinuria can be detected by laboratory techniques such as SDS-polyacrylamide gel gradient electrophoresis (SDS-PAGE) or immunoelectrophoresis.With the aid of these methods, only a qualitative determination of the light chain proteins is possible. Quantitatively, the Bence-Jones proteins can be determined by nephelometry. In nephelometry, the concentration of precipitated particles is measured by passing light through a cuvette containing an opacified liquid.
Complications
Bence-Jones proteinuria occurs primarily in the setting of multiple myeloma or plasmacytoma. In this tumor disease, there is severe emaciation of the bone, making it more prone to fracture and debris. In particular, the vertebral bodies are also affected, and important nerve tracts can be endangered. As a result of the disease, the body no longer produces enough important antibodies that are responsible for defending against pathogens. This makes the body more susceptible to infections, which can even be fatal. As the tumor also grows in the bone marrow area, this is displaced and there may be a deficiency of important blood cells such as platelets (thrombocytes), which are responsible for clotting. This prolongs the bleeding time in affected individuals. Therapy can also cause serious complications, as the chemotherapeutic agents used cannot distinguish between cancerous and healthy cells, thus damaging both. As a result of an extremely high excretion of Bence-Jones proteins, kidney failure (renal insufficiency) can occur. The kidney can no longer perform its functions and substances to be excreted by the kidney remain in the body in high concentrations, so that blood poisoning can develop (uremia). This can lead to a coma and ultimately to the death of the patient. Anemia as a result of kidney failure is also quite conceivable, since hormones produced by the kidney for blood formation are missing.
When should you see a doctor?
In most cases, the symptoms and complaints of Bence-Jones proteinuria are not particularly characteristic and therefore do not directly indicate the disease. For this reason, a doctor should be consulted if the symptoms of this disease persist over a long period of time. Especially in case of persistent bone pain or back pain, a doctor should be consulted. Fatigue and loss of performance can also be indicative of Bence-Jones proteinuria and should therefore be examined by a doctor. Most affected individuals also continue to suffer from fever and sudden weight loss as a result of the disease. Increased susceptibility to various infections and inflammations must also be investigated by a medical professional to possibly diagnose the disease. Usually, the general practitioner can be consulted for Bence-Jones proteinuria. This person can diagnose the disease. Further treatment is provided by other specialists. The earlier the disease is diagnosed, the higher the life expectancy of the affected person.
Treatment and therapy
Treatment of Bence Jones proteinuria depends mainly on the underlying disease. In some cases, no therapy is necessary at all. This is true in cases such as monoclonal gammopathy of uncertain significance (MGUS). MGUS is also not defined as a disease. Often, the concentration of light chain proteins formed in this case is so low that no further impairment results. However, regular medical check-ups should be carried out if MGUS is present. In approximately one to one and a half percent of all monoclonal gammopathies of unclear significance, multiple myeloma or other lymphomas may develop. Multiple myeloma is treated palliatively by chemotherapy with various chemotherapeutic agents. Curative therapy is possible with the help of bone marrow transplantation. However, not all forms of this disease are suitable for stem cell transplantation from bone marrow. Bone resorption is slowed down with the administration of biphosphonates. Infections should be treated immediately with antibiotics and, if necessary, with administration of immunoglobulins. In cases of severe kidney damage, regular dialysis is necessary. Waldenström’s disease is treated with medication. It is usually a palliative treatment to delay the course of the disease. Drug therapy often makes it possible to extend survival by as much as decades.
Outlook and prognosis
Bence Jones proteinuria has an unfavorable prognosis.In many cases, treatment is no longer necessary because the patient’s immune system is already severely weakened. The disease develops as a sequelae of an already existing tumor disease. The treatment of the cancer simultaneously has an effect on the fight against the Bence-Jones proteinuria. Nevertheless, the therapy is very costly for the organism and associated with numerous complications. Often, the patient’s remaining natural resources are not sufficient to initiate treatment. Nevertheless, medical care is currently the only way to improve the state of health. With alternative methods or the self-healing powers of the body, no recovery takes place. There is a threat of the patient’s demise. The organism already has a very low defense function at the onset of the disease. The antibodies are no longer produced independently to a sufficient degree due to the present cancer. In most cases, a bone marrow transplant must be performed to cure the underlying disease and Bence-Jones proteinuria. If this treatment is successful, the patient’s chances of recovery increase. Nevertheless, the mortality rate remains very high. In addition, the tumor disease may recur or further metastases may have formed in the body. In many cases, permanent and irreparable kidney damage occurs.
Prevention
No specific recommendations can be made for the prevention of Bence-Jones proteinuria. Environmental factors such as ionizing radiation, contact with herbicides, or even the corresponding genetic predisposition are considered risk factors for multiple myeloma. In general, however, a healthy lifestyle can reduce the risk of cancer. Regular medical checkups should be performed if MGUS is present.
Here’s what you can do yourself
Bence Jones proteinuria does not necessarily require treatment. Therapy focuses on alleviating the underlying monoclonal gammopathy. Nevertheless, adjunctive measures are useful. The patient should first take measures to promote renal activity. These include the copious intake of fluids as well as a healthy and balanced diet. Alcohol, caffeine and other substances that put a strain on the kidneys should be avoided. In the case of a severe course, curative therapy is indicated. In consultation with the physician, it may be advisable, for example, to initiate palliative therapy. This includes, for example, rest. In the later stages of the causative disease, a stay in a specialized clinic or nursing home may be necessary. Since Bence-Jones proteinuria is often due to radiation or chemotherapy, a recurrence or even an intensification of the existing symptoms cannot be completely ruled out by renewed treatment. However, the physician may consider alternative treatment options. For example, in some cases, radiation therapy can be replaced by surgical removal of a tumor. Patients should contact the physician in charge and discuss further steps with him or her.
