Kappa/Lambda Ratio in Kidney Disease: eGFR Reference Ranges

The serum kappa/lambda free light chain ratio is an important laboratory marker used when evaluating monoclonal gammopathies, including MGUS, multiple myeloma, AL amyloidosis, and monoclonal gammopathy of renal significance. However, kidney function has a major influence on serum free light chain concentrations.

As estimated glomerular filtration rate, or eGFR, declines, both kappa and lambda free light chains may accumulate in the blood even when no abnormal plasma-cell clone is present. This means that a result flagged as abnormal against the conventional kappa/lambda ratio of 0.26–1.65 may not be abnormal for a person with chronic kidney disease.

Large population-based evidence now supports interpreting the free light chain ratio in relation to eGFR rather than applying one universal reference interval to every patient. Proposed kidney-adjusted ranges from the iStopMM study are:

These are proposed central 99% reference intervals derived using the Freelite assay. They should not automatically replace the range reported by the testing laboratory, and they are not diagnostic thresholds for cancer.

Key points

• The kidneys are a principal route of free light chain clearance.
• Reduced eGFR commonly increases both kappa and lambda concentrations.
• Kappa often rises relatively more than lambda as kidney function declines, producing a modest upward shift in the ratio.
• A high kappa concentration with a ratio inside an appropriate kidney-adjusted interval is not, by itself, evidence of multiple myeloma.
• An abnormal ratio must be assessed together with absolute kappa and lambda values, eGFR, serum electrophoresis, immunofixation, urine findings, symptoms, and changes over time.
• Reference intervals depend on the assay used and are not necessarily interchangeable between laboratory platforms.

What are kappa and lambda free light chains?
Immunoglobulins, or antibodies, are produced by plasma cells. Each immunoglobulin contains heavy chains and one of two types of light chains:

• kappa, written as κ;
• lambda, written as λ.

Plasma cells normally produce a small excess of light chains that are not incorporated into complete immunoglobulin molecules. These circulating proteins are called serum free light chains, or sFLCs.
The serum free light chain test generally reports three results:

1. free kappa light chain concentration;
2. free lambda light chain concentration;
3. the kappa/lambda ratio.

The ratio helps determine whether one light chain type is being produced disproportionately. A markedly kappa-dominant pattern may suggest a kappa-restricted plasma-cell clone, while a markedly lambda-dominant pattern may suggest a lambda-restricted clone.
However, the ratio is a signal of imbalance, not a diagnosis. Kidney clearance, inflammation, immune activation, analytical methodology, and patient age can all affect the result.


Why kidney function affects free light chains
Free light chains are small enough to be filtered by the glomeruli and subsequently metabolized within the proximal tubules. When filtration declines, their removal from the circulation becomes slower and serum concentrations rise.
Kappa free light chains are generally produced as smaller monomers, while lambda chains are more likely to form dimers. Under normal renal function, the smaller kappa molecules are cleared more rapidly. As renal function worsens and nonrenal clearance becomes proportionally more important, the serum pattern increasingly reflects the higher physiological production rate of kappa chains.
The result is usually:

• an increase in free kappa;
• an increase in free lambda;
• and a modest shift of the kappa/lambda ratio toward kappa.

This process can occur without monoclonal gammopathy or hematologic malignancy. In the iStopMM CKD cohort, both absolute free light chain concentrations and the ratio increased as eGFR declined.
Polyclonal elevation versus monoclonal elevation
A polyclonal elevation occurs when many different plasma-cell populations produce immunoglobulins or when normally produced free light chains are not cleared efficiently. Kidney dysfunction, infection, inflammation, and autoimmune activity may contribute to this pattern.
A monoclonal elevation occurs when one plasma-cell or B-cell clone produces a disproportionate amount of one light chain type.
The distinction cannot reliably be made from the kappa concentration alone. The absolute kappa and lambda values, their ratio, the assay used, kidney function, serum and urine immunofixation, and the broader clinical picture must be considered together.

The conventional kappa/lambda reference range
The traditional serum kappa/lambda ratio used by many laboratories is:
0.26–1.65
The commonly quoted conventional absolute ranges are approximately:

• kappa: 3.3–19.4 mg/L;
• lambda: 5.7–26.3 mg/L.

These intervals were originally derived from a relatively small reference cohort of 282 people with normal kidney function. They remain widely reported, but their application to patients with reduced eGFR can result in unnecessary abnormal flags.

In the iStopMM analysis of participants with eGFR below 60 mL/min/1.73 m² and no evidence of monoclonality:

• 60% had kappa values above the conventional upper limit;
• 21% had lambda values above the conventional upper limit;
• 9% had a ratio outside 0.26–1.65.

This illustrates why absolute free light chain elevations are extremely common in CKD and why the conventional ratio can generate false-positive interpretations when kidney function is ignored.

The older renal reference range: 0.37–3.10
Before the eGFR-stratified iStopMM intervals were proposed, a broader “renal reference range” of:
0.37–3.10
was commonly used for patients with eGFR below 60 mL/min/1.73 m².
This range remains incorporated into the interpretive practice of some laboratories. It was an important improvement over applying 0.26–1.65 to every patient, but it treats all stages of reduced kidney function as one group.
An individual with an eGFR of 58 and an individual with an eGFR of 18 may have substantially different free light chain clearance. A single CKD interval may therefore be less precise than an eGFR-stratified model.

eGFR-adjusted kappa/lambda ratio ranges
The iStopMM study screened more than 75,000 participants using serum protein electrophoresis, immunofixation, and free light chain testing. Its CKD analysis included 6,461 participants with eGFR below 60 mL/min/1.73 m² who were not receiving kidney replacement therapy and had no evidence of monoclonality.
The investigators proposed the following central 99% reference intervals:

The investigators combined participants with eGFR 15–29 and below 15 because the number of participants with eGFR below 15 was too small to derive a separate statistically reliable interval.

Important limitations of this table
These values should be interpreted carefully:

• They were derived using Freelite reagents.
• They are statistical reference intervals, not cancer diagnostic cutoffs.
• They were calculated in people without detected monoclonality.
• The principal analysis excluded patients receiving dialysis.
• They should not be applied uncritically during acute kidney injury or rapidly changing renal function.
• Laboratories may continue to report different validated local or assay-specific ranges.

The iStopMM investigators excluded creatinine measurements associated with suspected acute kidney injury. Therefore, these ranges are most relevant when kidney function is sufficiently stable for eGFR to meaningfully represent the patient’s current renal state.

What about people with eGFR of 60 or higher?
Kidney function is not the only variable affecting free light chain distributions. Age also matters.
A 2025 iStopMM analysis proposed revised intervals for people with preserved kidney function:

Applying the older reference intervals produced substantially more presumed light-chain MGUS diagnoses. The revised age-stratified definition reduced the estimated prevalence of light-chain MGUS by 82% in the study population. None of the participants who were reclassified as not having light-chain MGUS progressed to a lymphoproliferative disorder during the reported follow-up period.

These findings do not mean that every laboratory has adopted the revised intervals. They show that the interpretation of free light chains is evolving and that kidney function, age, and analytical method should be included in the assessment.

Does a high kappa/lambda ratio in CKD mean multiple myeloma?
No. A high ratio is not, by itself, a multiple myeloma diagnosis.

In CKD, modest elevations may result from altered clearance. The probability that a result reflects monoclonal production depends on several factors:

• how far the ratio lies outside the appropriate assay- and eGFR-specific interval;
• whether kappa or lambda is disproportionately elevated;
• the absolute concentration of the involved light chain;
• serum protein electrophoresis findings;
• serum and urine immunofixation;
• hemoglobin, calcium, creatinine, and eGFR;
• proteinuria and albuminuria;
• symptoms and organ involvement;
• and the direction and speed of change over time.

Multiple myeloma is diagnosed using a combination of clonal plasma-cell evidence, myeloma-defining events, biomarkers, imaging, and evidence of organ damage. A free light chain result must therefore be placed within a complete hematologic assessment.

When an abnormal result needs further investigation
Further assessment is particularly important when an abnormal free light chain pattern is accompanied by one or more of the following:

• a ratio outside an appropriate kidney- and assay-adjusted interval;
• a clearly disproportionate increase in one light chain;
• a monoclonal protein identified by electrophoresis or immunofixation;
• unexplained decline in eGFR;
• significant or increasing proteinuria;
• hematuria without another explanation;
• unexplained anemia;
• hypercalcemia;
• persistent bone pain or pathological fractures;
• unexplained peripheral neuropathy;
• cardiomyopathy or other features raising suspicion for amyloidosis;
• recurrent infections, weight loss, or marked constitutional symptoms.

These findings do not establish a plasma-cell disorder, but they can change the urgency and scope of the evaluation.

Kappa/lambda ratio and monoclonal gammopathy of renal significance
Monoclonal gammopathy of renal significance, or MGRS, refers to kidney injury caused by a nephrotoxic monoclonal immunoglobulin produced by a B-cell or plasma-cell clone that does not necessarily meet the criteria for an overt hematologic malignancy.

This distinction is clinically important. A clone may be small, while the immunoglobulin it produces can still cause substantial kidney damage.

A normal or only mildly abnormal free light chain ratio does not independently exclude MGRS. When the clinical presentation suggests a monoclonal kidney lesion, the diagnostic evaluation may include:

• serum protein electrophoresis;
• serum immunofixation;
• serum free light chains;
• urine electrophoresis and immunofixation;
• quantification and characterization of urinary protein;
• hematologic assessment;
• and, when appropriate, kidney biopsy.

The International Kidney and Monoclonal Gammopathy Research Group identifies kidney biopsy as central to establishing the diagnosis of MGRS and defining the specific renal lesion.

Recommended testing context
A clinically meaningful interpretation of free light chains in kidney disease generally requires more than three numbers.
Kidney assessment
Relevant measurements include:

• serum creatinine;
• eGFR;
• urine albumin-to-creatinine ratio;
• urine protein-to-creatinine ratio or measured total protein;
• urinalysis for blood and other abnormalities;
• previous creatinine and eGFR values;
• and evidence of acute versus chronic kidney dysfunction.

KDIGO defines and stages CKD using both kidney filtration and markers of kidney damage, especially albuminuria. An eGFR value should therefore not be considered in isolation from urine findings and the clinical timeline.
Monoclonal protein assessment
Depending on the clinical question, testing may include:

• serum protein electrophoresis;
• serum immunofixation;
• quantitative immunoglobulins;
• serum free kappa and lambda chains;
• urine protein electrophoresis;
• urine immunofixation;
• complete blood count;
• calcium;
• and additional hematologic, imaging, or tissue investigations when indicated.

For patients with multiple myeloma and renal impairment, International Myeloma Working Group recommendations include serum creatinine, eGFR, serum free light chains, and 24-hour urine assessment with electrophoresis and immunofixation.

A practical interpretation algorithm
Step 1: Identify the assay and laboratory range
Check which analytical platform was used and use the laboratory’s validated reference interval as the initial point of comparison.

Step 2: Establish current kidney function
Review eGFR, creatinine, previous results, and whether renal function is stable. Avoid treating an eGFR-adjusted CKD interval as definitive during acute kidney injury.

Step 3: Examine all three free light chain results
Do not interpret kappa, lambda, or the ratio separately.
Ask:

• Are both chains elevated?
• Is one chain disproportionately elevated?
• Is the ratio inside the appropriate renal interval?
• How large is the absolute involved free light chain concentration?

Step 4: Look for independent evidence of monoclonality
Review serum electrophoresis, serum immunofixation, quantitative immunoglobulins, and relevant urine testing.

Step 5: Assess kidney injury pattern
Evaluate albuminuria, total proteinuria, hematuria, eGFR trajectory, and whether the pattern is typical for diabetes, hypertension, medication effects, glomerular disease, or a possible monoclonal process.

Step 6: Compare with previous results
A stable mildly abnormal result may have a different meaning from a rapidly widening ratio or rising involved free light chain concentration.

Step 7: Integrate clinical findings
Laboratory interpretation should account for age, inflammation, infection, autoimmune disease, medication exposure, hematologic findings, and symptoms.

Step 8: Refer when appropriate
A patient may require hematology, nephrology, or combined evaluation when there is persistent monoclonal evidence, unexplained kidney injury, significant proteinuria, a ratio clearly outside the renal interval, or clinical suspicion of myeloma, amyloidosis, or MGRS.

Free light chain ratios in hemodialysis
Patients receiving dialysis require separate consideration. Absolute free light chain concentrations may be markedly elevated, and the measured values can be influenced by:

• residual kidney function;
• dialysis timing;
• membrane type;
• dialysis efficiency;
• assay methodology;
• and the interval between sessions.

A 2024 study of 137 stable patients receiving conventional thrice-weekly high-flux hemodialysis proposed:
Kappa/lambda ratio: 0.55–1.75
The samples were collected before a midweek dialysis session, and free light chains were measured using the Freelite assay on an Optilite analyzer. The authors suggested that modern high-flux membranes may clear middle molecules sufficiently to produce a ratio closer to the non-CKD range.
This interval should not be generalized to every dialysis patient. It comes from a single-center cohort using a specific assay, blood-sampling schedule, and high-flux dialysis approach. Peritoneal dialysis, different filters, acute dialysis, residual kidney function, and alternative laboratory methods may produce different patterns.

Why assay methodology matters
Free light chain measurements are not fully standardized across all laboratory platforms.
Available assays use different antibodies, calibration systems, and analytical technologies. Comparative studies have found meaningful differences in absolute kappa and lambda concentrations and in calculated ratios, especially at abnormal concentrations.
Results from Freelite, N Latex, and Sebia assays should therefore not automatically be treated as interchangeable. This is particularly important when:

• applying published reference ranges;
• monitoring a patient over time;
• assessing response to treatment;
• or interpreting thresholds originally validated with a different assay.

Whenever possible, serial monitoring should use the same laboratory and analytical method. A change in assay can create an apparent biological change that is partly or entirely analytical.

Reference interval does not mean diagnostic cutoff
A reference interval describes the distribution expected in a defined reference population. It does not determine whether an individual does or does not have a disease.
Therefore:

• a value outside the interval is not proof of monoclonal gammopathy;
• a value inside the interval does not exclude every plasma-cell or kidney disorder;
• the magnitude of the abnormality matters;
• associated tests matter;
• and trends matter.

The revised iStopMM ranges are valuable because they may reduce false-positive classifications. An independent Danish MGUS cohort subsequently found that patients reclassified as having a normal ratio using the revised age- and renal-function-adjusted intervals did not have a significantly greater progression risk than patients whose ratios were normal under both definitions. The revised intervals improved risk stratification while reducing unnecessary high-risk classification.

Why longitudinal interpretation matters
A single blood test is a snapshot. A series of results can reveal:

• gradual parallel elevation of kappa and lambda as eGFR declines;
• progressive dominance of one light chain;
• a widening ratio;
• a response to treatment;
• or an apparent change caused by a new laboratory method.

For example, a modestly elevated kappa level with a stable ratio and stable eGFR may represent a different risk pattern from a rapidly rising kappa concentration, widening ratio, new proteinuria, and declining eGFR.
Longitudinal interpretation is especially important in patients with:

• MGUS;
• smoldering multiple myeloma;
• treated multiple myeloma;
• AL amyloidosis;
• MGRS;
• kidney transplantation;
• or chronic dialysis.

How Aima Diagnostics approaches free light chain interpretation
Aima Diagnostics is designed to interpret laboratory findings as interconnected patterns rather than isolated high or low values.
For a kappa/lambda result, a context-aware analytical system can evaluate:

• the reported assay and reference range;
• kappa and lambda concentrations;
• the calculated ratio;
• creatinine and eGFR;
• albuminuria and proteinuria;
• hemoglobin and calcium;
• markers of inflammation;
• related electrophoresis and immunofixation findings;
• medications and clinical background;
• and longitudinal changes.

This approach can help distinguish a pattern compatible with reduced renal clearance from one that may warrant closer evaluation for monoclonal production.
AI-supported interpretation does not establish a diagnosis and should not replace a hematologist, nephrologist, laboratory specialist, kidney biopsy, bone marrow examination, or other clinically indicated investigation. Its role is to organize complex data, identify relationships, and support more informed medical review.

Frequently Asked QuestionsWhat is the normal kappa/lambda ratio with kidney disease?
There is no single universally accepted ratio for every patient with kidney disease. The older renal interval is 0.37–3.10. The iStopMM study proposed eGFR-specific intervals of 0.46–2.62 for eGFR 45–59, 0.48–3.38 for eGFR 30–44, and 0.54–3.30 for eGFR below 30 mL/min/1.73 m². These proposed intervals were derived using the Freelite assay and are not universal diagnostic cutoffs.

Can CKD cause high kappa free light chains?
Yes. Reduced kidney clearance commonly increases serum kappa free light chains. In the iStopMM CKD cohort, 60% of participants without detected monoclonality had kappa levels above the conventional upper reference limit.
What does it mean when both kappa and lambda are high?
When both are elevated and the ratio remains within an appropriate renal interval, reduced kidney clearance or polyclonal immune activation is often more likely than a monoclonal plasma-cell disorder. The result still needs to be interpreted alongside eGFR, inflammation, electrophoresis, immunofixation, urine findings, and clinical history.

Can kidney disease make the kappa/lambda ratio high?
Yes. As renal function declines, kappa and lambda clearance changes, and the ratio may shift modestly upward. This is why applying the conventional upper limit of 1.65 to patients with CKD may produce false-positive results.
Is a kappa/lambda ratio of 2 abnormal in CKD?
It depends on eGFR, age, assay, absolute kappa and lambda concentrations, and the laboratory’s reference interval. A ratio of 2 may be above the conventional range of 0.26–1.65 but still within the proposed iStopMM interval for an individual with eGFR below 60.

Can a normal renal ratio exclude multiple myeloma or MGRS?
No. A ratio inside a renal reference interval decreases suspicion for a strongly light-chain-restricted pattern but cannot independently exclude multiple myeloma, MGRS, AL amyloidosis, or another monoclonal disorder. Other blood tests, urine studies, imaging, bone marrow evaluation, or kidney biopsy may be required depending on the presentation.
What tests should accompany an abnormal free light chain ratio?
Common companion tests include creatinine, eGFR, complete blood count, calcium, serum protein electrophoresis, serum immunofixation, quantitative immunoglobulins, urine protein measurement, urine electrophoresis, and urine immunofixation. The exact evaluation depends on the degree of abnormality and the clinical context.

Should the test be repeated?
Repeat testing may be appropriate when the result is mildly abnormal, kidney function is changing, an acute illness is present, or confirmation of a trend is clinically important. The timing should be determined by the treating clinician because a patient with a minor stable abnormality requires a different approach from one with rapidly declining eGFR, substantial proteinuria, or a markedly abnormal ratio.

What is the kappa/lambda ratio range during hemodialysis?
A 2024 single-center study proposed a range of 0.55–1.75 for stable patients receiving high-flux hemodialysis, with blood collected before the midweek session. This result is method- and dialysis-specific and should not automatically be applied to all dialysis populations.

Conclusion
Kidney function is one of the most important determinants of serum free light chain concentrations. As eGFR declines, both kappa and lambda commonly increase, and the kappa/lambda ratio may shift upward without a monoclonal plasma-cell disorder.
For this reason, the conventional ratio of 0.26–1.65 should not be interpreted mechanically in patients with chronic kidney disease. eGFR-adjusted reference intervals provide a more precise framework, but they remain assay-dependent statistical ranges rather than standalone diagnostic thresholds.
The most reliable interpretation combines:

• absolute kappa and lambda concentrations;
• the kappa/lambda ratio;
• eGFR and creatinine trajectory;
• albuminuria and proteinuria;
• electrophoresis and immunofixation;
• hematologic findings;
• symptoms and organ involvement;
• and longitudinal change.

The central question is not simply whether a result is marked “high.” It is whether the complete laboratory pattern is proportionate to the patient’s kidney function or suggests biologically disproportionate production of one light chain.


Selected scientific references

1. Long TE, et al. Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study. Blood Cancer Journal. 2022.
2. Long TE, et al. New Definition of Light Chain Monoclonal Gammopathy of Undetermined Significance. JAMA Oncology. 2025.
3. Peña C, et al. Reference interval of free light chains ratio in patients with end-stage renal disease on chronic hemodialysis. Haematologica. 2024.
4. Levin A, et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International. 2024.
5. Leung N, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nature Reviews Nephrology. 2019.
6. Schieferdecker A, et al. Comparison of three different serum-free light-chain assays—implications on diagnostic and therapeutic monitoring of multiple myeloma. Blood Cancer Journal. 2020.
7. Maeng CV, et al. Revised free light chain reference intervals enhance risk stratification in monoclonal gammopathy of undetermined significance and reduce overdiagnosis. Blood Cancer Journal. 2025.

Last updated: July 2026
Medical review: A.Berg and L.Levenberg
Editorial disclaimer: This material is intended for professional education and general information. It does not provide an individual diagnosis and is not a substitute for assessment by a qualified healthcare professional.