A 65-year-old man with multiple myeloma (IgA-λ type) presents with acute kidney injury (creatinine 3.2 mg/dL). To determine whether light chain cast nephropathy (myeloma kidney) is the cause, which investigation is most specific?

Explanation

## Diagnostic Investigation for Myeloma Kidney (Light Chain Cast Nephropathy) **Key Point:** Renal biopsy with light microscopy and immunofluorescence is the gold standard for confirming light chain cast nephropathy (myeloma kidney) and distinguishing it from other causes of acute kidney injury in myeloma. ### Pathology of Myeloma Kidney Light chain cast nephropathy is characterized by: - **Intratubular casts** composed of monoclonal light chains (λ > κ) - **Tubular epithelial cell injury** and apoptosis - **Interstitial inflammation** and fibrosis (chronic cases) - Immunofluorescence shows **monotypic light chain** (κ or λ only, not both) ### Diagnostic Approach to AKI in Myeloma | Investigation | Findings in Myeloma Kidney | Diagnostic Value | |---|---|---| | Serum free light chain ratio | Elevated involved/uninvolved ratio | Supports diagnosis; not specific | | 24-hour urine light chains | Elevated (often >1 g/day) | Supportive; not diagnostic | | Urine dipstick/microscopy | May show proteinuria, granular casts | Non-specific; casts may not be visible | | **Renal biopsy (LM + IF)** | **Intratubular casts + monotypic IF** | **Gold standard; definitive diagnosis** | **High-Yield:** Light chain cast nephropathy accounts for ~50% of AKI in myeloma. Other causes include: - Acute tubular necrosis (ATN) from hypercalcemia, dehydration - Acute interstitial nephritis (drug-related) - Glomerulonephritis (AL amyloidosis, immunoglobulin deposition disease) **Clinical Pearl:** Immunofluorescence is crucial because it demonstrates **monotypic** light chain deposition (only κ or only λ), confirming clonal origin and excluding polyclonal proteinuria. **Warning:** Serum and urine light chain assays are elevated in myeloma kidney but are NOT specific—they can be elevated in other kidney diseases and do not prove cast nephropathy. Biopsy is needed to visualize intratubular casts. **Mnemonic: Renal Biopsy in Myeloma** — **L**ight microscopy (casts), **I**mmunofluorescence (monotypic), **M**onoclonal origin confirmed = Diagnostic.