Quickly identify patients at risk from kidney damage
Free light chains are nephrotoxic
Figure 1. Myeloma Kidney.
The kidney is often affected in plasma cell dyscrasias, usually due to the effects of nephrotoxic monoclonal free light chains. Monoclonal light chains produced by different individuals have different nephrotoxic properties. For example, some monoclonal light chains may form fibrils (AL amyloidosis), whilst others may form deposits localised to the renal basement membranes (light chain deposition disease) or the tubulo-interstitium (cast nephropathy).
At presentation, approximately 50% of Multiple Myeloma (MM) patients have renal impairment, varying from mild (asymptomatic) to severe renal insufficiency. 12 - 20% of MM patients present with acute renal failure. The majority of cases are caused by cast nephropathy, also known as "myeloma kidney". In cast nephropathy free light chains, in association with Tamm-Horsfall protein, form waxy deposits that block the distal tubules, Figure 1.
10% of all MM patients will remain on long-term haemodialysis and for these individuals there is a high mortality rate and treatment options are limited.
Improve screening protocols for monoclonal gammopathy
Freelite can be used in conjunction with serum protein electrophoresis, to rapidly screen for monoclonal gammopathy in those patients presenting with unexplained renal impairment.
Figure 2. Adapted from figure originally published in "Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure"
BMC Nephrology 2008;9:11 doi: 10.1186/1471-2369-9-11
The highly sensitive Freelite assay quantifies kappa (κ) and lambda (λ) free light chain levels using a routine serum sample and can eliminate the need to perform urine Bence Jones Protein (BJP) analysis.
In monoclonal gammopathy associated with severe renal insufficiency, e.g. cast nephropathy, reductions in glomerular filtration rate (GFR) lead to reduced urine output. Therefore, the concentrations of urinary free light chains do not reflect serum concentrations and production. One major advantage of the Freelite assay in such cases is that the serum κ/λ ratio is little affected by renal function. With renal insufficiency, kappa and lambda concentrations rise but the κ/λ ratio will usually remain within normal limits1.
A recent study proposes using an extended reference range for the κ/λ ratio in patients with renal impairment2. Using this extended range, diagnostic specificity of the Freelite assays increased whilst maintaining it's high sensitivity3,4.
- Adding Freelite to the initial investigation of patients in the renal clinic could improve detection of monoclonal gammopathies
- Freelite can replace urine Bence Jones protein analysis for the diagnosis of monoclonal gammopathies
- Using an extended renal reference κ/λ ratio can improve diagnostic specificity
Improve monitoring of monoclonal gammopathy
Figure 3. Increase in serum FLC before an increase in serum creatinine. After treatment serum creatinine levels fell but to a higher level than baseline indicating some residual damage to the kidney. Courtesy of S. Abdalla, St. Mary's Hospital, London, UK.
Monitoring serum FLC levels in monoclonal gammopathy patients may identify those individuals at risk of light chain mediated renal damage. The case study in Figure 3 demonstrates increasing FLC concentrations that precede renal impairment (measured by serum creatinine). It can be speculated that the rising concentrations of FLC contributed to the increasing renal impairment. This case highlights the benefit of the Freelite assay to identify patients at risk of renal impairment.
Improve monitoring of haemodialysis
Extended haemodialysis on the Gambro protein-leaking HCO 1100 dialyzer has been shown to efficiently and safely remove large amounts of free light chains from the serum5. In this initial study three out of five patients with acute renal failure caused by cast nephropathy treated with the HCO 1100 in combination with chemotherapy became dialysis independent.
A further prospective pilot study6 assessed the combination of standard chemotherapy with extended haemodialysis, using a high cut-off dialyser (HCO-HD), on serum free light chain (FLC) concentrations and renal recovery in patients with biopsy-proven cast nephropathy and dialysis-dependent acute renal failure.
Out of 19 patients who met the study entry criteria, 13 received uninterrupted chemotherapy and extended HCO-HD and demonstrated sustained reductions in serum FLC concentrations and recovered renal function. Of the 6 patients who had chemotherapy temporarily withheld or discontinued, early reductions in serum FLC concentrations were not sustained and only one subsequently became independent of dialysis. A multi-centre, randomised control trial has commenced to address the hypothesis that extended HCO-HD increases the percentage of patients with cast nephropathy who become independent of dialysis.
- Download literature - A new lifeline for myeloma kidney patients - MKG500.E
- Download Spanish literature - Una nueva oportunidad para pacientes con riñón de mieloma - MKG538.E
A 2009 Nature Reviews publication7 entitled 'Serum free light chain assessment in monoclonal gammopathy and kidney disease' by Colin A. Hutchison, Kolitha Basnayake and Paul Cockwell is available to order below.
Interview
Read an interview with Guillermo Herrera, MD, Professor and Chairman, Dept. Pathology, St Louis University, USA for his view on the utility of serum free light chain assays in renal disease.
The Kidney in Plasma Cell Dyscrasias
Editor: G.A. Herrera, St. Louis, Mo.
Contributions to Nephrology, volume 153. Published by Karger.
"In recent years, the knowledge of how renal damage occurs in patients with plasma cell dyscrasias/myeloma has substantially increased. For the first time, this publication brings together issues relating to the diagnosis and pathogenesis of these disorders, as well as a summary of advances achieved in the treatment and management of patients."
Request your copy here.
