Light chain deposition disease (LCDD)

• monoclonal immunoglobulin (Ig) deposition disease (MIDD) is characterized by deposition of monoclonal Ig in the kidney as well as other organs and tissues, including the heart, liver, and nerve fibers
  • three subtypes of MIDD have been described: light chain deposition disease (LCDD), heavy chain deposition disease, and light and heavy chain deposition disease
    • of these, LCDD is the most common
    • LCDD is associated with a lymphoproliferative disorder, most commonly multiple myeloma (LCDD is an uncommon monoclonal gammopathy which should be considered carefully in patients who have both renal disease and a lymphoplasmacytic disorder capable of producing monoclonal light chains - myeloma, macroglobulinaemia, lymphoma, chronic lymphatic leukaemia)
      • remaining cases develop LCDD either without a prior history of monoclonal gammopathy or in the setting of progression of monoclonal gammopathy of unknown significance (MGUS) without evidence of MM
      • most patients with LCDD present with proteinuria and renal insufficiency. About 50% of patients have nephrotic syndrome but as many as 25% of patients have less than 1 g of proteinuria per day
        • in 15% to 30% of patients, there is no demonstrable monoclonal gammopathy by serum (SPEP) or urine (UPEP) protein electrophoresis
• LCDD is a systemic disease with frequent cardiac, hepatic and gastrointestinal involvement patients usually present with the nephrotic syndrome (NS) or asymptomatic proteinuria with renal impairment which may be progressive and rapidly so in some cases
• diagnosis
  • straightforward when monoclonal light chains are present in the serum and/or urine and the renal biopsy shows characteristic morphological changes and stains clearly for kappa or lambda light chains
  • often difficult as patients may not have a known or demonstrable lymphoplasmacytic disorder, monoclonal light chains may be detectable only intermittently and at low concentrations in the serum and/or urine and the demonstration of light chains in the renal biopsy may be difficult even with specific monoclonal light chain antibodies due to high non-specific background staining
  • diagnosis should be confirmed or excluded by repeated immune electrophoresis (IEP) or immunofixation of serum and concentrated urine specimens for monoclonal light chains, histological examination with immunostaining of the bone marrow, lymphoid tissue and the renal biopsy for kappa and lambda light chains
  • renal biopsy reveals nodular glomerulosclerosis in some 50% of the nephrotic patients and 25% of the non-nephrotic patients
    • most of the remaining biopsies show changes similar to MCGN but without Ig or C deposits and 10% show only mesangial changes
• treatment and prognosis
  • median survival time from diagnosis is some 18 months
    • evidence that chemotherapy, especially if started early, slows progression to chronic renal failure and postpones death from the extra renal manifestations of LCDD and from the underlying lymphoplasmacytic disorder
    • 1-year survival on haemodialysis of patients with chronic renal failure due to LCDD is some 20% and a few patients have received kidney transplants with occasional long-term survivors and with recurrence of LCDD in the kidney transplant

Reference:

• 1. Buxbaum J, Gallo J.Nonamyloidotic monoclonal immunoglobulin deposition disease. Light-chain, heavy-chain, and light- and heavy-chain deposition diseases, Hematol Oncol Clin North Am 1999: 1235
• 2. Buxbaum J et al. Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Ann Intern Med 1990;112: 455
• 3. Hall CL, Peat DS. The Interesting Case Light chain deposit disease: a frequent cause of diagnostic difficulty. Nephrol Dial Transplant (2001); 16: 1939-1941.