OVERVIEW

What is heavy chain deposition nephropathy?

Heavy chain deposition nephropathy (HCDN) is a renal manifestation of heavy chain deposition diseases (HCDD), first reported by Tubbs in 1992. HCDD is a type of monoclonal immunoglobulin deposition diseases (MIDD). MIDD is a group of immune system disorders characterized by the deposition of monoclonal immunoglobulins and their free fragments—light chains (LC) and/or heavy chains (HC)—in various tissues and organs, leading to dysfunction of the affected organs. The kidneys are most commonly involved, with clinical symptoms primarily manifesting as nephropathy. Other organs such as the heart, liver, skin, and nervous system may also be affected. MIDD can be classified into three types: light chain deposition disease (LCDD), light and heavy chain deposition disease (LHCDD), and heavy chain deposition disease (HCDD). The cause of HCDD remains unclear but may be related to immune dysfunction. Currently, chemotherapy is often used to alleviate symptoms, though the prognosis is generally poor.

Is heavy chain deposition nephropathy common?

HCDD is relatively rare. A 2001 study retrospectively analyzed 7,241 and 5,443 cases of kidney disease, diagnosing HCDD in only 6 (0.08%) and 1 (0.02%) cases, respectively. The disease is more common in individuals over 50 years old, with the youngest reported case being 26 years old. No significant gender difference has been observed. HCDN is even rarer, with only about 100 cases reported domestically.

What are the types of heavy chain deposition nephropathy?

Based on different heavy chain antigens, this disease can be classified into γ, α, μ, δ, and ε heavy chain deposition nephropathy. γ heavy chain disease can be further divided into γ1, γ2, γ3, and γ4; α heavy chain into α1 and α2; and μ heavy chain into μ1 and μ2.

Is heavy chain deposition nephropathy hereditary?

No.

SYMPTOMS

What are the common manifestations of heavy chain deposition nephropathy?

• Common symptoms of heavy chain deposition nephropathy include hypertension, edema, proteinuria, hematuria, and renal insufficiency. Most patients rapidly deteriorate and progress to end-stage renal disease.

• Most patients show no obvious manifestations of hematologic diseases but may have hypocomplementemia. About 12% of cases are secondary to multiple myeloma, and these patients may test positive for Bence Jones protein in urine.

• Rare cases involve skin manifestations such as cutis laxa or present primarily with arthropathy.

Can heavy chain deposition nephropathy lead to renal failure?

A few patients experience symptom relief after treatment, but most rapidly deteriorate and progress to end-stage renal disease. Prognosis depends on disease stage, and aggressive chemotherapy may improve renal function and complement levels in early-stage HCDN patients, thereby improving outcomes.

CAUSES

What are the possible causes of heavy chain deposition nephropathy?

The etiology of heavy chain deposition nephropathy is currently not fully understood. It may be related to the deposition of heavy chains in the kidneys, triggering immune reactions with various renal cells, leading to corresponding nodular sclerosis and global sclerosis.

DIAGNOSIS

How is heavy chain deposition nephropathy diagnosed?

The definitive diagnosis of heavy chain deposition nephropathy requires a combination of clinical manifestations, laboratory tests, and most importantly, renal biopsy pathology obtained through kidney puncture, confirmed by light microscopy, immunohistochemistry, and transmission electron microscopy.

What tests are needed for heavy chain deposition nephropathy?

• First, routine blood tests are required, including complete blood count, rheumatology panel, ANCA, thyroid function, glycated hemoglobin, tumor markers, immunoglobulin complement, hepatitis panel, and serum/urine light chains to rule out other secondary causes.

• If the patient is suspected of having secondary multiple myeloma, a bone marrow biopsy should also be performed.

• The gold standard for diagnosing HCDN is renal biopsy pathology.

What precautions should be taken for kidney biopsy?

Kidney biopsy is a very important procedure in nephrology. Local anesthesia is administered during the procedure, and patients need to hold their breath during the puncture, which is generally tolerable with minimal pain.
Postoperatively, it is important to keep the puncture site clean and dry. Avoid heavy physical activity for 1–3 months after the procedure, monitor urine color, blood pressure, and other vital signs, and follow up with urinary tract ultrasound.

What precautions should be taken for bone marrow biopsy in heavy chain deposition nephropathy?

Local anesthesia is used during bone marrow biopsy, and the procedure is generally not very painful. Before the procedure, patients should be asked about coagulation disorders or the use of anticoagulants. Postoperatively, the puncture site should be kept clean and dry, and water contact should be avoided for 3 days.

What are the pathological features of heavy chain deposition nephropathy?

MIDD (monoclonal immunoglobulin deposition disease) has similar pathological changes. Light microscopy reveals diffuse nodular glomerulosclerosis. Immunopathology shows linear deposition of a single type of light chain (LC) and/or heavy chain (HC) along the tubular and glomerular basement membranes. Electron microscopy reveals non-fibrous, granular electron-dense deposits.
The hallmark of HCDN is the deposition of only HC in the kidneys, with LC being negative. All reported cases of HCDN exhibit diffuse glomerular nodular sclerosis.

What diseases should heavy chain deposition nephropathy be differentiated from?

Heavy chain deposition nephropathy should be differentiated from diseases with similar pathological manifestations, including diabetic nephropathy, membranoproliferative glomerulonephritis, amyloid nephropathy, cryoglobulinemic nephropathy, diffuse mesangial proliferative glomerulonephritis, and other types of MIDD.

TREATMENT

Which department should I visit for heavy chain deposition disease (HCDD)?

You can visit the nephrology department at your local hospital.

How is heavy chain deposition disease treated?

Currently, there is no particularly effective treatment. Different chemotherapy regimens are used depending on the type of heavy chain deposition:

• γ-HCDD: Patients may receive different treatments based on disease severity, typically including melphalan, prednisone, cyclophosphamide, vincristine, or doxorubicin.

• α-HCDD: Without prompt treatment, the disease usually progresses rapidly. Antibiotics are the first-line therapy. If ineffective after 3 months, chemotherapy (similar to lymphoma regimens) is used, such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or MOPP (mechlorethamine, vincristine, procarbazine, prednisone).

• μ-HCDD: Due to its rarity, limited research exists. Current treatments often include prednisone, cyclophosphamide, or vincristine.

Will chemotherapy for HCDD cause hair loss, nausea, or vomiting?

Chemotherapy is challenging because it targets both malignant and healthy cells, often causing nausea and vomiting. Doctors typically prescribe antiemetics to alleviate symptoms, but patients may still experience poor appetite or loss of taste. Hair loss is less common and mainly associated with vincristine—hair regrows after treatment ends.

Can heavy chain deposition disease be cured?

No, it can only be managed. Most patients eventually develop chronic kidney disease, progressing to end-stage renal failure (commonly known as uremia).

DIET & LIFESTYLE

What should patients with heavy chain deposition kidney disease pay attention to in terms of diet and lifestyle?

High-quality low-protein diet.
Preferred high-quality proteins include eggs, milk, fish, and other animal proteins; protein intake should be controlled at 0.6–0.8 g/kg/day. For example, if a patient weighs 50 kg, they should consume 30–40 g of protein per day. One egg contains about 6–7 g of protein, while 100 g of fish contains 13–19.5 g of protein, depending on the type. Reduce salt and other condiments, and consume moderate amounts of soy products.

PREVENTION

Can Heavy Chain Deposition Disease Be Prevented?

This disease is a malignant condition, and its progression is often irreversible. The goal of prevention can only be to delay further deterioration and prolong the patient's life. What patients and doctors can do is actively pursue symptomatic treatment, pay attention to daily diet, and for those with renal dysfunction—especially those progressing to end-stage renal failure—dialysis or kidney transplantation may be necessary.