Treatment of Cast Nephropathy in Multiple Myeloma

Pathophysiology and Diagnosis

Cast nephropathy occurs when excess monoclonal free light chains interact with Tamm-Horsfall protein in the loop of Henle, forming obstructive casts that damage renal tubules 1, 2
Serum free light chain concentrations >80-200 mg/dL significantly increase risk of acute kidney injury, with higher levels correlating with greater risk 2
Diagnostic workup should include serum creatinine, electrolytes, estimated glomerular filtration rate, 24-hour urine collection, serum electrophoresis, and serum free light chain measurement 3
Renal biopsy may not be necessary if proteinuria predominantly consists of light chains with high serum free light chain levels, but should be considered when the etiology is unclear 3

Correct reversible factors first, including hypercalcemia, volume depletion, and hyperuricemia; discontinue nephrotoxic medications 1, 3
Stratify treatment approach based on involved free light chain levels 1
The National Comprehensive Cancer Network recommends correcting reversible factors and discontinuing nephrotoxic medications before initiating treatment 3

Bortezomib-based regimens should be initiated immediately as they do not require dose adjustment in renal impairment and can be safely used in dialysis patients 3, 4
The American Society of Clinical Oncology recommends bortezomib-based regimens as first-line therapy for cast nephropathy 4
Target >50% reduction of involved free light chain from baseline and a free light chain level <50 mg/dL by the end of cycle 1 1, 4
Bortezomib is preferred as it is not renally cleared or nephrotoxic 4
Lenalidomide requires dose adjustment based on renal function 3
Pomalidomide 4 mg/day appears safe in all degrees of renal impairment, including dialysis 3, 4

For patients with free light chain >150 mg/dL, daily plasma exchange should be added to chemotherapy 1
Plasma exchange can reduce serum free light chain levels by 45-75% per session 1
High cut-off hemodialysis is an alternative to plasma exchange that can remove 60-75% of free light chains per session 1
The International Myeloma Society recommends plasma exchange or high cut-off hemodialysis for patients with high free light chain levels 1

Renal recovery is associated with improved overall survival 2
Factors associated with renal recovery include lower baseline creatinine 3 and ≥50% drop in serum free light chain levels 4
Early mortality remains higher in patients without kidney recovery despite treatment 2