DDx for Acute Kidney Injury in Myeloma Patients

Multiple myeloma and renal disease often go hand-in-hand, and it has a differential diagnosis which is fascinating in terms of its breadth. Although we often diagnosis many of these patients with "cast nephropathy", my suspicion is that some of the more rare etiologies listed below are underdiagnosed since kidney biopsies in these patients are often not performed on account of significant comorbidities or the fact that often the treatment (myeloma-specific therapy) would be the same regardless.

Here is the differential diagnosis that I keep in my mind when seeing a patient with multiple myeloma:
1. "Cast Nephropathy": caused by precipitation of monoclonal light chain with Tamm-Horsfall protein and subsequent tubular obstruction. Lambda light chains are most likely to cause cast nephropathy. Often when the terms "myeloma kidney" is used, "cast nephropathy" is the implied mechanism. These patients may also have an undetectable urine protein on dipstick (which detects only albumin) but a high 24-hour urine protein (which detects all protein).

2. Light Chain Deposition Disease: caused by glomerular damage by deposition of serum light chains within the glomerulus. In contrast to cast nephropathy, LCDD is usually (85%) due to kappa light chains rather than lambda light chains. The light microscopy is characterized by nodular glomerulosclerosis (often similar in appearance to amyloidosis or diabetic disease) but can be differentiated from amyloid by its lack of Congo red staining. These patients will often demonstrate nephrotic syndrome.

3. Amyloidosis: caused by deposition of circulating paraprotein as amyloid fibrils, which appear as birefringent staining with Congo Red. As in LCDD, patients with amyloidosis may demonstrate nephrotic-range proteinuria, and other organ systems (e.g. restrictive cardiomyopathy) may also be involved.

4. hypercalcemia-induced AKI: patients with myeloma often present with hypercalcemia as a result of osteolytic lesions that can result in acute kidney injury, best treated with fluids, bisphosphonates, and lasix once volume-replete.

5. hypovolemia: in my experience these patients are very susceptible to volume depletion, and often demonstrate decreased po intake when getting chemotherapy or when developing progressive disease.

6. tumor lysis syndrome: rarely, patients with a large tumor burden will develop hyperuricemia and resultant tumor lysis syndrome when initiated on anti-myeloma therapy.

7. hyperviscosity syndrome: this is rare in multiple myeloma and more commonly occurs in IgM paraproteinemias such as Waldenstrom's macroglobulinemia, but can result in renal disease.

8. bisphosphonate-induced renal failure: many patients with hypercalcemia related to myeloma are treated with bisphosphonates, which have an interesting renal side effect profile. Specifically, pamidronate is associated with a collapsing FSGS/nephrotic syndrome picture, whereas zoledronic acid is associated with ATN which can progress to ESRD.

9. Fanconi's syndrome: proximal tubule dysfunction induced by paraproteinemias can result in a type II RTA.

That's a long list!