Renal Failure

Today we had a fantastic discussion regarding causes of renal failure secondary to multiple myeloma.

To summarize:
Hypercalcemia
Hypercalcemia (as a consequence of bone destruction) can predispose a patient to renal failure in 3 ways. First, high calcium levels lead to a diuretic effect, reducing the effective circulating volume. Second, calcium can deposit into the kidney itself (nephrocalcinosis). Finally, the high calcium levels can precipitate in the collecting system leading to stone disease.

Stones
In addition to calcium based stones, the high cell turnover also predisposes the patient to form uric acid stone (gouty nephropathy). This can also be nephrotoxic.

Cast Nephropathy
Filtration of toxic light chains leads to both tubular injury and intratubular cast formation (and obstruction). The light chains bind avidly to the normal tubule mucoprotein (Tamm-Horsfall) and lead to obstruction. As the tubule becomes damaged, adult onset Fanconi Syndrome, a proximal type 2 RTA, can develop (loss of amino acids, glucose and ability to acidify the urine).

Light Chain Deposition Disease
Excess monoclonal light chains deposit in the kidney (without forming fibrils) and can lead to a nephrotic type syndrome.

Amyloid
Circulating light chains are taken up by macrophages where they are partially processed, then excreted as Congo-red positive, beta-pleated fibrils. These are nephrotoxic.

Recurrent Infections
Both systemic overwhelming infections (sepsis) and recurrent urologic infections are more common in myeloma patients which put them at risk for renal failure.

NSAIDS
Bone pain hurts. Patients often turn to NSAIDS to help manage the pain and this can lead to renal failure in a number of ways (will be discussed in a future blog).

Renal Vein Thrombosis
MM is a hypercoagulable state (loss of anti-thrombin 3 in the urine). The renal vein is susceptible to thrombosis and subsequent renal failure.

The "anti-kidney" antibody
Multiple antibodies against various "kidney-ness" have been described (evil-humors?) and associated with renal failure.

Cord Compression
Plasmacytoma love the spinal cord and as a consequence, cord compression can develop. A real emergency!

Pretty impressive list. If I missed something, add it to the comment section. Also, check out this article from JASN.