In a 73‑year‑old woman with chronic kidney disease (creatinine 1.8 mg/dL, β‑2‑microglobulin 5.4 mg/L), heart failure with reduced ejection fraction, normal serum protein electrophoresis and urinary kappa/lambda free‑light‑chain ratio >4, are these abnormal findings attributable to the CKD rather than a monoclonal gammopathy?

Diagnostic Interpretation: Elevated Urinary Kappa/Lambda Ratio in CKD

The elevated urinary kappa/lambda ratio >4 in this patient is most likely attributable to chronic kidney disease rather than a monoclonal gammopathy, given the normal serum protein electrophoresis, absence of proteinuria/albuminuria, and elevated β2-microglobulin consistent with impaired renal clearance. 1, 2, 3

Understanding the Free Light Chain Abnormality

Why CKD causes this finding:

• Chronic kidney disease profoundly affects free light chain metabolism because both kappa and lambda chains are normally cleared by glomerular filtration and catabolized by proximal tubular cells 3
• With a creatinine of 1.8 mg/dL (estimated GFR approximately 30-40 mL/min/1.73m²), this patient has CKD stage 3b, which significantly impairs free light chain clearance 1, 4
• The elevated β2-microglobulin (5.4 mg/L) confirms reduced glomerular filtration, as β2-microglobulin is also cleared renally and rises proportionally with declining kidney function 3
• Critically, 42.5% of CKD patients without multiple myeloma demonstrate abnormal kappa/lambda ratios, making this a common and largely nonspecific finding in renal impairment 5

Why monoclonal gammopathy is unlikely:

• Normal serum protein electrophoresis effectively excludes significant monoclonal protein production, as this test would detect intact immunoglobulins or large monoclonal spikes 1
• The absence of proteinuria or albuminuria argues strongly against light chain deposition disease, cast nephropathy, or AL amyloidosis—all of which typically present with significant proteinuria (often nephrotic range) 1, 6
• The International Myeloma Society emphasizes that while urinary kappa/lambda ratios can be abnormal in CKD, the serum free light chain ratio is the critical discriminator for clonality 1, 2

Essential Next Steps to Confirm or Exclude Monoclonal Disease

Mandatory serum testing:

• Obtain serum free light chain assay (kappa and lambda) with calculated ratio—this is the single most important test to distinguish CKD-related elevation from clonal disease 1, 2
• The normal serum kappa/lambda ratio in CKD with GFR 30-44 mL/min/1.73m² is 0.48-3.38 (not the standard 0.26-1.65 used for normal renal function) 4
• If the serum ratio falls within this adjusted range, monoclonal gammopathy is effectively excluded 1, 2
• Perform serum immunofixation electrophoresis to definitively rule out small monoclonal proteins that might be missed on standard electrophoresis 1

Additional hematologic evaluation:

• Complete blood count to assess for anemia, thrombocytopenia, or other cytopenias suggestive of bone marrow involvement 2
• Serum calcium level (hypercalcemia suggests myeloma) and quantitative immunoglobulins (immunoparesis suggests plasma cell disorder) 2
• If serum free light chain ratio is highly abnormal (≥100 for kappa or ≤0.01 for lambda), immediate bone marrow biopsy is indicated regardless of other findings 2

Interpreting the Cardiac Context

Heart failure considerations:

• The moderately reduced ejection fraction with unknown etiology raises the possibility of cardiac amyloidosis, though this typically presents with preserved (not reduced) ejection fraction 2
• NT-proBNP at 400 pg/mL is elevated but NT-proBNP ≥332 ng/L (332 pg/mL) has >99% sensitivity for cardiac AL amyloidosis involvement, so this level warrants attention 2
• However, cardiac amyloidosis would almost certainly produce significant proteinuria (typically >5 g/day), which is absent in this patient 1
• The combination of heart failure, CKD, and diabetes type 2 is sufficient to explain the NT-proBNP elevation without invoking infiltrative disease 1

Critical Pitfalls to Avoid

Common errors in interpretation:

• Do not assume malignancy based solely on abnormal urinary light chain ratios in the setting of CKD—the serum ratio is the definitive test 2, 5
• Do not use standard reference ranges (0.26-1.65) for serum free light chain ratios in patients with reduced GFR; apply CKD-adjusted ranges 1, 4
• Recognize that different free light chain assays (FreeLite vs. N Latex) have different performance characteristics and are not interchangeable—the N Latex assay is less affected by renal impairment 1
• Avoid ordering bone marrow biopsy prematurely—this is only indicated if serum studies reveal monoclonal protein, highly abnormal serum free light chain ratio, or CRAB criteria (hypercalcemia, renal failure, anemia, bone lesions) 2

Determining the Cause of CKD

Most likely etiologies in this patient:

• Diabetic nephropathy is the leading consideration given type 2 diabetes, though the absence of albuminuria is atypical for classic diabetic kidney disease 1
• Approximately 30-40% of diabetic patients with reduced GFR lack significant albuminuria, representing non-proteinuric diabetic kidney disease 1
• Hypertensive nephrosclerosis related to heart failure and chronic hypertension (implied by heart failure diagnosis) is another strong possibility 1
• The combination of diabetes, heart failure, and age 73 years creates a high-risk profile for CKD progression regardless of the specific histologic pattern 1

When kidney biopsy would be indicated:

• If serum studies reveal monoclonal protein with abnormal free light chain ratio, biopsy would be essential to diagnose specific monoclonal immunoglobulin-related kidney disease 1
• If unexplained rapid progression of kidney function occurs, or if active urinary sediment (hematuria, cellular casts) develops 1
• Currently, biopsy is not indicated given the clinical picture consistent with diabetic/hypertensive CKD and absence of features suggesting acute glomerular disease 1

Monitoring Strategy

If serum free light chains are normal or proportionally elevated:

• Repeat serum free light chain assay and serum protein electrophoresis at 6 months to confirm stability 2
• Continue annual monitoring if results remain stable, as the risk of progression to symptomatic myeloma in true MGUS is approximately 1% per year 2
• Optimize management of diabetes and heart failure with evidence-based therapies including SGLT2 inhibitors (proven kidney and cardiovascular benefit in this population) 1
• Avoid nephrotoxic medications (NSAIDs, aminoglycosides) and use caution with iodinated contrast agents given CKD stage 3b 1, 2