Monday, February 11, 2013

Dialysis for cast nephropathy

I love being a clinical nephrologist. One of the great things about the job has been the non-clinical activities that have burrowed their way into my schedule. In the last 12 months I have:
  • Judged resident research day
  • Taught renal physiology to second year medical students (back to the class room for the first time in a decade)
  • Worked on the scientific advisory board for the National Kidney Foundation of Michigan
  • Attended the editorial board meeting of the American Journal Kidney of Kidney Disease
  • Participated in a mock FDA new drug approval meeting
  • Implemented an EMR and patient portal for my practice
These events, in addition to my regular teaching gigs and taking care of patients, keep my work interesting. 

Last week, I had another novel experience. One of my medical school colleagues, who is now a myeloma expert, asked me to review a case and write a letter in support of a request for "compassionate-use" exception for an unapproved dialyzer. He wanted to use the Gambro HCO 1100 dialyzer, the Nimbus 2000 of dialyzers.
What makes the HCO1100 unique is the exceptionally large pore size. Cast nephropathy is the predominant cause of acute renal failure in multiple myeloma. Removing the offending agent, serum free light chains should have an ameliorating effect on the kidney injury. Previously we have used plasmapheresis to treat this, however this is not beneficial. The HCO1100 is able to effectively remove particles with a molecular weight up to 45,000 daltons and Hutchison et al showed that it can actually dialyze free light chains from the serum. Look at the following clearance data from Hutchison:
The second from the last column on the right has the clearance data.

The Gambro CHO1100 is literally orders of magnitude better than the competition. Hutchison looked at clearance data by examining light chains in the discarded dialysate, this avoided confusion from light chains absorbed to the membrane. Absorption removes light chains from the serum but requires frequent replacing the dialyzer.

The same group followed that paper with an uncontrolled case series of patients, all with biopsy-proven, dialysis-dependent, cast nephropathy. Each was treated with the protocol established by the previous paper* and they had excellent results. Nineteen patients received the therapy. Fourteen of them were able to receive uninterrupted chemotherapy and all fourteen recovered renal function (became dialysis independent). The five who had interruptions to their chemo regimen all remained dialysis dependent. The interruptions were all due to infections and all of these patients died during follow up.
Renal recovery in green, renal non-recovery in red.
The most recent data (good coverage here) I'm aware of comes from Heyne et al. They also published on 19 patients with biopsy proven cast nephropathy. All of the patients were treated on the same chemotherapy regimen which was based on bortezo­mib (Velcade) rather than the various regimens used in the Hutchison series. They too, found a 75% renal recovery. I'm waiting for the PDF of the article because of the Springer paywall (grr).

Definitive information on how effective this therapy is should come from the EuLITE trial which is expected to have results this year. Ironic that some of the only RCT data in nephrology will come from the hematologists.

If you are interested in this you should take a look at Amyloid Planet's excellent post on suffering from Theralite Envy.

* for those interested the dialysis protocol calls for daily 8 hour treatments. They used 2 HCO1100 placed in series to increase the surface are up to about 2 meters squared. They ran the blood flows at 250 ml/min and the dialysate at 500 ml/min. Dialysis was run daily for 5 days then every other day for 12 days then for 6 hours three days a week.

Update: above I mentioned my frustration with the Springer Paywall and four different readers sent me the PDF. Thank-you. Nice to live in a networked world.
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