Renal Biopsy Case Discussion
September, 1995

Pathologic diagnosis:

MYELOMA CAST NEPHROPATHY

Follow up:

Confirmatory laboratory data included identification of monoclonal kappa light chains in the urine and a bone marrow biopsy that demonstrated 80% plasma cells.

Discussion of Case by Dr. Jennette

The patient presented with severe renal failure. The normal renal size by ultrasound was evidence against advanced chronic disease. The differential diagnosis of the acute renal failure would have included acute tubular necrosis and hypersensitivity tubulointerstitial nephritis. Acute or rapidly progressive glomerulonephritis would have been unlikely given the minor degree of hematuria and proteinuria. In retrospect, the anemia, elevated sedimentation rate and advanced age of the patient may have positioned myeloma cast nephropathy relatively high in the differential diagnosis, but these findings are certainly nonspecific. Hypercalcemia would have been somewhat more suggestive, but was not present. In an older patient with acute renal failure, should serum and urine always be analyzed for monoclonal immunoglobulin molecules prior to renal biopsy?

Even if the evidence for multiple myeloma had been known, would a renal biopsy have been of value for confirming the presence of myeloma cast nephropathy versus some other cause for ARF, or some other type of myeloma- induced renal disease? Multiple myeloma and other B-cell dyscrasias cause a variety of renal injury in addition to myeloma cast nephropathy; e.g., AL amyloidosis, light chain deposition disease, and, rarely, renal failure secondary to parenchymal infiltration by neoplastic B-lymphocytes or plasma cells. The absence of substantial proteinuria made AL amyloidosis and light chain deposition disease unlikely in this patient.

The pathologic findings in the biopsy specimen were diagnostic for myeloma cast nephropathy; i.e., angular and fractured casts with adjacent multinucleated giant cells by light microscopy and preferential staining for one light chain by immunofluorescence microscopy. The casts of myeloma cast nephropathy have much more angular edges and are more often fractured than the casts usually observed with other renal diseases; and typically have adjacent reactive cells including occasional multinucleated giant cells. There was no evidence for other types of paraprotein-induced renal disease.

There is a very nice recent review of myeloma cast nephropathy by Christopher Winerals of the UK in Kidney International (1). Of the last 42 patients with myeloma-associated ARF seen in the Oxford Renal Unit, Dr. Winerals notes that in 18 patients the diagnosis of multiple myeloma was made by the nephrologists, as in the patient under discussion. Of the 42 patients, 29 had no identifiable precipitating cause for the ARF, while 8 had hypercalcemia and 4 had recently taken NSAIDs. In patients with multiple myeloma, NSAIDs are incriminated in the precipitation of ARF, and this may have been the case in the patient under discussion.

Dr. Winerals suggests that treatment for myeloma cast nephropathy ARF has three important components:

  1. Limit cast formation by counteracting any precipitating factors such as correcting dehydration or hypercalcemia, discontinuing NSAIDs, and treating infections; and inducing alkaline diuresis with a goal of >3 liters/day of urine at a pH of approximately 7 if the patient can tolerate fluid volume expansion.
  2. Reduce elevated paraprotein concentration, e.g. with chemotherapy (usually an alkylating agent and corticosteroids) and possibly plasmapheresis.
  3. Early institution of dialysis. Approximately 50% of patients with myeloma cast nephropathy ARF will regain renal function.

Reference

  1. Winerals CG. Acute myeloma kidney. Kidney Intern 48:1347-1361, 1995

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