Myeloma and the Kidney

Ryan Sanford2.22.2010

How Often is the Kidney Involved

Symptomatic MM: CRAB– hyperCalcemia– Renal dysfunction– Anemia– Bone lesions

1/5 to 2/5 patients with MM have renal involvement

What Does it Signify?

At presentation– SCr < 1.5 80% alive at 1 year– SCr > 2.3 50% alive at 1 year

Renal Improvement to MM Treatment also favorable

The Immunoglobulin

Light Chains come in lambda and kappa

A Few General Points First

The Proteins of MM– Light chains (LC) almost always the problem– Various potential proteins to be produced

Intact immunoglobulins +/- Light Chains and Heavy Chains

The SPEP: – Not a good test to identify LCs– Increased sensitivity if coupled with serum immunofixation– Can only quantify LCs with direct assessment

The UPEP– Prior to serum free light chain assessment, the UPEP was the test

of choice to find LCs

The Light Chain (LC)

aka Bence Jones proteins– Monoclonal– A ratio of κ:λ

Freely filtered, absorbed in PCT The LC biochemical properties determines

the type, if any, of renal disease

The Serum Free Light Chain Assessment

Polyclonal ABs directed at hidden LC epitopes (when a full Ig) used for sensitive quantification of κ and λ light chains

Coupled with SPEP more Sn/Sp than SPEP/UPEP

Could be replacing UPEP as test of choice

What Types of Involvement

Light chain cast nephropathy – Myeloma Kidney [>40% of cases]

Light chain deposition disease [<10%] Primary AL Amyloidosis [<10%] Also: Hypercalcemia, interstitial nephritis,

acquired Fanconi’s syndrome, GN

Proteinuria in MM

Albuminuria [a grossly positive U/a for protein]– If positive:

Nonspecfic glomerular leak, nephrosis LCDD or Amyloidosis

– If negative: other proteins or no protein in urine; cast nephropathy

Addition of Sulfosalicylic Acid to Supernatant– If bland sediment and minimal protein on U/a– Precipitates all urinary protein– If positive suggestive of light chains in urine

Cast Nephropathy / Myeloma Kidney

Acute or Chronic Worsened by volume depletion Two mechanisms

– Intratubular casts and obstruction LC has affinity for Tamm-Horsfall protein (secreted in

thick AL) See casts in distal nephron

– Direct tubular toxicity U/a: trace/no protein; bland sediment

With the Microscope

LC Cast with Obstruction

Treatment of Cast Nephropathy

Chemotherapy to reduce LC production Aggressive hydration Plasmapheresis?

– Rapid removal of toxic LC– Contentious– If beneficial – best for those with high levels of

LCs, severe renal failure, and firm diagnosis of cast nephropathy

AL Amyloidosis

LC uptake, processing, and secretion by macrophages

Secretion product precipitates into β-pleated fibrils, becoming Congophilic

Nephrosis and progressive loss of GFR

Light Chain Deposition Disease

Similar to AL Amyloidosis, except no fibril formation of Congophilic staining

Nephrosis and progressive loss of GFR

Tubular Malfunction

LCs reabsorbed in PCT and accumulate– Fanconi Syndrome

Phosphate wasting Proximal RTA [type 2] Hypouricemia Glycosuria Proteinuria Hypokalemia and hypochloremia

References

UpToDate.com Hutchison, C.A. et al. Nat Rev Nephrol.

Serum free light chain assessment in monoclonal gammopathy and kidney disease. 5, 621-627 (2009)