Pathogenesis and diagnosis of light chain cast nephropathy (myeloma kidney)
- Gerald B Appel, MD
Gerald B Appel, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
- Nelson Leung, MD
Nelson Leung, MD
- Professor of Medicine
- Mayo Clinic College of Medicine
- S Vincent Rajkumar, MD
S Vincent Rajkumar, MD
- Edward W. and Betty Knight Scripps Professor of Medicine
- Mayo Clinic
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Robert A Kyle, MD
Robert A Kyle, MD
- Section Editor — Plasma Cell Disorders
- Professor of Medicine
- Mayo Medical School
The term myeloma kidney or light chain cast nephropathy refers to a disorder in which monoclonal urinary immunoglobulin light chains (Bence Jones proteins) lead to acute or chronic renal failure [1-3]. (See "Types of renal disease in multiple myeloma".) By definition, the diagnosis of light chain cast nephropathy indicates the presence of multiple myeloma; in other words, it is considered a "myeloma-defining event" . Light chain cast nephropathy can occur as the first manifestation of myeloma or can develop later during the course of myeloma.
This topic provides a review of the pathogenesis and diagnosis of light chain cast nephropathy. Overviews of the renal diseases associated with multiple myeloma and the therapy of acute renal failure (ARF) in multiple myeloma are discussed separately. (See "Types of renal disease in multiple myeloma" and "Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases" and "Treatment of kidney disease in multiple myeloma".)
Light chain cast nephropathy is caused by large amounts of monoclonal free light chains (MFLCs) produced in multiple myeloma . Light chains are freely filtered across the glomerulus and then largely reabsorbed by the proximal tubular cells. The normal rate of light chain excretion is <30 mg/day. However, reabsorptive capacity can be exceeded due to overproduction in multiple myeloma, resulting in an increase in light chain excretion that can range from 100 mg to >20 g/day.
The risk of light chain cast nephropathy is directly related to the urinary free light chain (FLC) concentration and the type of light chains . In an analysis of 2592 patients enrolled in multicenter myeloma trials, kidney injury developed in up to 54 percent of patients who had a very high concentration of urinary FLC (defined as >12 g/g creatinine) but in ≤2 percent of patients with no urinary light chains . The risk of renal failure was approximately 8 to 18 percent among those who had urinary light chains of 0 to 4 g/g creatinine and 29 to 38 percent among those who had urinary light chains of 4 to 12 g/g creatinine. However, urinary FLC measurements are rarely used in clinical practice since the test is unreliable. The methods used to estimate MFLC are the serum free light chain (SFLC) assay and the 24-hour urine protein electrophoresis. (See 'Diagnosis' below and "Recognition of monoclonal proteins".)
Light chain cast nephropathy is uncommon in patients with low (<1500 mg/L) SFLC concentrations [8,9].
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- Light chain cast nephropathy
- Tubular injury
- CLINICAL MANIFESTATIONS
- Serum free light chain assay
- Urine 24-hour protein quantitation and electrophoresis
- Serum protein electrophoresis and immunofixation
- Differential diagnosis
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS