Light chains are small polypeptide proteins that are synthesized by plasma cells and are components of immunoglobulins. Usually, these light chains are found in a very small quantity in urine since either they are expelled by the kidney or metabolized by the organ. They are present in urine when light chain synthesis rises or nephrons of tubules fail to recover them. 

In LCDD, the characteristic presentation is nodular glomerulosclerosis which should be differentiated from diabetic nephropathy under the electron microscope. ‘Bence Jones protein’ also falls under the umbrella of urinary protein that forms a precipitation at 56°C and dissolves again at 100°C, having the characteristics of monoclonal light chains originating from a single plasma cell clone. These proteins are related to different systemic illnesses. 

Light-chain nephropathy, which was first described by Smithline et al. in 1976, is the renal disease caused by light-chain proteinuria. This condition encompasses various glomerular abnormalities caused by the deposition of monoclonal immunoglobulins and is classified into: 

Organized Deposits: 

• Fibrillar: Seen in amyloidosis 
• Microtubular: Associated with cryoglobulinemia and immunotactoid glomerulonephritis 

Nonorganized, Granular Deposits: 

• Monoclonal Immunoglobulin Deposition Disease, also referred to as monoclonal gammopathy. 

Proteinuria in a form of light-chain, depends on the circumstances, is more prevalent in males and light-chain nephropathy is ten times higher among men than women. Monoclonal gammopathies are age related and are found in 1 to 5% of individuals over the age of 65. 

In multiple myeloma, Bence Jones protein (BJP) is detected in 47 to 70% of cases; it is higher in IgA 71% and IgD 100%. Multiple myeloma commonly develops in men over the age of 70 with very few cases being reported in those under the age of 40. 

BJP is most often diagnosed in males between 40 and 66 years old and is present in 30 to 40% of patients with WM. In primary amyloidosis, BJP is detected in 92% of patients and its frequency is significantly higher in men and patients with a median age of 59 to 63 years. 

Light chains are formed as components of immunoglobulins and are usually metabolized or excreted in the urine by the kidneys. Kappa light chains are relatively small and very easy to filter while the larger chains of lambda can hardly be filtered. Injury to renal tissues gives rise to the filtration of these proteins with related diseases such as proteinuria. 

Light chains cause diseases including light-chain deposition disease (LCDD) or amyloidosis when they deposit in the organs such as the kidneys. For this reason, their ability to harm the kidney may depend on their biochemical characteristics although this is not clearly known. 

Light chains in toxic concentration may cause dysfunction of kidney tubule known as Fanconi syndrome. In LCDD, kappa chains seem to play a role in disease progression by stimulating matrix accumulation. Amyloidosis is associated with light chains (AL amyloid) and chronic infections (AA amyloid), and other causes related to the misfolding of proteins. The cause of development and further formation of amyloid deposits by light chains in amyloidosis has not yet been established, but the possible factors which may be responsible for it are believed to be the biochemical characteristics of light chains and chronic inflammation. 

The presence of light-chain proteins in the urine is seen in Multiple myeloma, Waldenström macroglobulinemia and amyloidosis. In multiple myeloma, the type of light chain involved varies by myeloma subtype: IgG, 60% of which were kappa chain; IgA, 71% of which were kappa chain; IgD, all of which were lambda chain. About 15 percent of the multiple myeloma are characterized by the secretion of only light chains, which is more malignant. 

Waldenström macroglobulinemia exhibits light-chain proteinuria in 30-40 % of the cases, associated with IgM paraproteins, amyloidosis exhibits light-chain proteinuria in 92 %, and most of them being lambda chains. Rare connections include diseases such as lymphoma, chronic lymphocytic leukemia and plasma cell leukemia. 

It may also be found in benign monoclonal gammopathy of uncertain significance with minor proteinuria, or due to rifampin intake. In monoclonal gammopathy of renal significance (MGRS), light chains are part of the molecules deposited in the kidney and cause renal dysfunction but do not warrant specific hematological therapy. 

The prognosis of light-chain proteinuria depends on the primary disease. The most frequent complication is renal failure, which depends on the concentration of light-chain protein. Chronic renal failure occurred more incidence than acute renal failure, and it was present in 30 to 60% of the cases compared to 8 to 30% incidence of acute renal failure. Light-chain multiple myeloma is summarized with renal insufficiency in more than half of patients and with deterioration of the indices at higher rates of light-chain excretion. 

Benign Monoclonal Gammopathy: Renal disease remains as a minor complication occurring in about 1 to 2% frequency in patients with mild manifestations such as proteinuria or hematuria. 

Light-Chain Deposition Disease (LCDD): The overall outcomes are usually unfavorable with high death rates frequently attributed to cardiovascular disease or complications of infection. Overall, one-year survival rate after post-chemotherapy is 90%, and the five-year survival rate is 70%, with lower renal survival rates. 

Multiple Myeloma: Infections and renal failure comprise two most frequent reasons for death. The prognosis is slightly worse in patients with renal failure; it is particularly poor in those with IgD myeloma. Poor prognostic markers include high tumor load, hypercalcemia and increased serum beta 2-microglobulin level. 

Amyloidosis: AL amyloidosis can be fatal, and the median of the overall survival is usually less the two years. However, treatment responders can have favorable outcomes with a median survival of 89.4 months. 

Age Group 

Middle-aged to Elderly Adults: Non-amyloid form of light-chain-related nephropathies which include the multiple myeloma; amyloidosis and light chain deposition disease (LCDD) are common in patients over the age of 50 years. The occurrence is age dependent, though relatively more frequent among the population of individuals above the age of 60 years. 

• Cachexia 
• Hypertension 
• Pallor 
• Dehydration 
• Edema 

• Multiple myeloma 
• Amyloidosis 
• Light chain deposition disease 

Chronic and Progressive: The renal disorders are generally characterised by the development of progressive, gradual reduction in the functioning of the kidneys. Patients may develop CKD over months to years. 

Acute Renal Failure: Sometimes, most especially in situations where light chain deposition is high or in cast nephropathy such as in multiple myeloma, there may be an acute onset deteriorating renal function sharply. This can be with the development of acute kidney injury (AKI) oligoanuric/anuric. 

Management of the Underlying Disease in Plasma Cell Dyscrasia 

Multiple Myeloma 

• Chemotherapy: They are usually in the form of bortezomib, lenalidomide, and dexamethasone (VRd) or cyclophosphamide, thalidomide and dexamethasone (CTD). 
• Stem Cell Transplant: High-dose chemotherapy further escalated by an auto-SCT could also be an option for qualified patients. 
• Monoclonal Antibodies: Some of the drugs include daratumumab or elotuzumab may be used together with other therapies. 

Amyloidosis 

• Chemotherapy: Certain treatments are like that of multiple myeloma (e. g., melphalan and dexamethasone), particularly in cases of light-chain amyloidosis. 
• Stem Cell Transplant: In some instances, this may be done through autologous stem cell transplant where feasible. 
• Supportive Care: Handling of side effects of amyloidosis for instance cardiac and gastrointestinal manifestations. 

Light-Chain Deposition Disease (LCDD) 

• Chemotherapy: The same regimens as those used for MM, comprising melphalan and prednisone have also been utilised. 
• Supportive Measures: Hypertension and other complications as well as the management of the symptoms. 

Management of Renal Complications 

Proteinuria 

• Angiotensin-Converting Enzyme (ACE) Inhibitors/Angiotensin II Receptor Blockers (ARBs): These medications are known to reduce proteinuria and as well assist in the preservation of renal function. 
• Diuretics: For use in the control of oedema and fluid balance. 

Renal Failure 

• Renal Replacement Therapy: The most specific indication for dialysis could be considered patients with considerable degree of renal dysfunction or end-stage renal disease. 
• Supportive Care: Some involve maintenance of adequate flow of potassium, sodium, magnesium and calcium, fluid levels and blood pressure. 

Acute Kidney Injury (AKI) 

• Immediate Treatment: Manage the cause, which may perhaps include using Chemotherapy or Plasmapheresis to help alleviate the light-chain burden. 
• Supportive Care: Principal focus encompasses power.and infusion therapy, electrolyte balance rehabilitation, assessment of kidney function. 

Supportive and Symptomatic Care 

• Management of Symptoms: Management of symptoms that are related to the underlying disease, for example, bone pain, anaemia, and peripheral neuropathy. 
• Nutritional Support: Monitoring and controlling dietary intake for the management of renal function and for the health of the patient with kidney disease. 

Monitoring and Follow-Up 

• Regular Assessment: Regular blood tests that check the patient’s renal function, light-chain levels, and progression concerning the treatment plan. 
• Adjustment of Therapy: Cessation of treatment or changing the kind of drugs, reduction of dose, switching from one therapeutic schedule to another. 

Nephrology

Protein Restriction: Avoiding high protein diets by limiting protein because high levels can increase the workload of the kidneys and proteinuria. A dietitian can create a diet plan that provides all the body requirements that will not so much as put pressure on the kidneys. 

Sodium and Fluid Restriction: Avoiding diets high in sodium that leads to increased blood pressure and fluid retention causes edema and hypertension. 

Potassium and Phosphorus Management: Supervising changes in potassium and phosphorus intake to avoid abnormalities in electrolyte balance, particularly in patients with decreased kidney function. 

Weight Management: Reducing the stress on the kidney through adherence to proper dietary measures, regular exercise, weight loss. 

Exercise: Promoting exercise tolerance for cardiovascular endurance, peripheral pulsation, and metabolic adjustment objectives. 

Nephrology

Bortezomib: It is the first proteasome inhibitor that was approved for use in the treatment of cancer. Proteasome is an enzyme complex exists in all cells of organisms and plays the role of degrading proteins which are marked for destruction, and these proteins are involved in controlling the cell cycle and thus the balance of cellular. Bortezomib is a proteasome inhibitor that selectively targets, of all the enzymes involved in intracellular protein degradation, the 26S proteasome and binds to it reversibly to cause degradation of proteins required for cancer cell survival and proliferation. Melphalan, prednisone, and bortezomib-based chemotherapy along with early plasmapheresis is effective in patients who have multiple myeloma complicated by kidney failure due to myeloma cast nephropathy. It can still result in a complete renal recovery in about 40% of the patients and is the best treatment modality in this case. 

Melphalan: It is an anticancer drug that belongs to alkylating agent group which cross-link DNA strands thus preventing mitosis. It is inactive against only resting cells but is active against both resting and proliferating tumor cells. 

Nephrology

Vincristine: It inhibits cell division because of affecting intracellular tubulin. It attaches to microtubules and spindle protein during the S phase of the cell cycle which leads to arrest of cell cycle. 

Doxorubicin: It works through the interacting with topoisomerase II and by the production of free radicals. These actions result in the destruction of DNA and prevention of cancer cells from proliferating in the body. 

Nephrology

Plasmapheresis: It is frequently employed in patients with multiple myeloma and acute kidney injury attributable to myeloma cast nephropathy. This procedure is especially useful if there is a requirement to rapidly shed light chains from the circulation to fill further damage to the kidneys. 

In plasmapheresis, the patient’s plasma that contains the dreaded light chains is taken out and replaced by donor plasma or a plasma substitute. This lowers the levels of light chains in the circulation and thus may be used to treat renal damage. 

Renal Biopsy: A renal biopsy may be required in patients with extracted light-chain-associated renal disorders to establish the type, severity and prognosis of the disease to appropriate treatment. It is a process in which a doctor removes some tissue from the kidney for examination under a microscope. Depending on the type of kidney disease, certain staining methods can reveal the presence of light-chain deposits, cast nephropathy, or any other associated renal pathology. 

Hemodialysis: It may be needed in patients with light-chain-associated renal diseases necessitating severe AKI or chronic kidney disease causing uraemia or fluid overload. Hemodialysis means that the blood of the patient is filtered through a machine to remove waste materials and excess fluids that the kidneys are unable to production. 

Nephrology

The management of light-chain-associated renal disorders consists of several steps. First, one must support the patient and stop the deterioration of the disease, which may require plasmapheresis, renal support, and chemotherapy. In chronic phase the focus is made on the management of the underlying plasma cell disorder and the maintenance of renal function with the help of additional courses of chemotherapy, supportive care, and follow-up. Therefore, the goal of remission is to manage the disease with the help of maintenance therapy and changes in the patients’ lifestyle. In the later stages, it lies on comprehensive care and focusing on symptom control as well as discussing issues like dialysis or transplantation for end-stage renal disease.