Tag: lupus

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Lupus nephritis, MMF and maintenance therapy

I love it when I have a clinical question and I’m able to find a well executed study that’s exactly fits my question. It’s like fitting the last piece of a puzzle.

A year ago I was referred a patient with heavy proteinuria. Initial assessment showed 7 grams of proteinuria, a cholesterol over 300, edema and an albumin of 0.7. Classic nephrotic syndrome.

Before he returned for his first follow-up appointment disaster struck. He developed chest pain and shortness of breath from a pulmonary embolism. This was a patient my age, two kids, professional. Looking at him was like looking in the mirror, but for the grace of G-d that could be me sitting in that exam chair.

black arrow points to tubuloreticular inclusions
seen in SLE and HIV.

After a month of anti-coagulation I was able to convince pulmonology and hematology to reverse the Coumadin for a few hours to get a kidney biopsy. It was membranous nephropathy with endothelial tubuloreticular inclusions. Along with consistent ANA and DS DNA we made a diagnosis of SLE WHO V and began mycophenolate mofetil. We titrated the MMF up to 3g a day and after 6 months he was in remission.

After a few months of sub nephrotic proteinuria, a normal albumin and a year of anti-coagulation he stopped his Coumadin. He has weaned his prednisone to 10 mg every other day and stopped the alendronate and rosuvastatin. Now he wants to get off the mycophenolate. Given how frightening the PE was, my preference would be to treat him forever. I casually surveyed my peers and got answers as varied as:

  • I never lower the MMF, every time I do the patient relapses
  • I taper it off after 6 months of remission

When I consulted the literature to look into this I found this paper:

Bingo. They maintained patients on MMF for 3 years at 2 grams a day with excellent results. 

Importantly there were no deaths, only 10% had serious infections and no cases of cancer occurred with the mycophenolate. 
Looks like an acceptably benign therapy with good outcomes.
Aside: While looking up how to spell endothelial tubuloreticular inclusions, I came across this paper (how I love you so Google) showing a significant number of patients with endothelial tubuloreticular inclusions that did not have lupus or HIV. I was taught that these EM findings were essentially pathognomonic for lupus. Interesting.
UPDATE: a second trial, the MAINTAIN trial (PDF), showed almost identical results. Included for completeness. 
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Journal Club: ECLIPSE Trial and Membranous Lupus

Clevipidine
Aronson et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg (2008) vol. 107 (4) pp. 1110-21

Clevipidine is a short-acting, IV, calcium channel blocker licensed for blood pressure control. The ECLIPSE Trial is a randomized, multi-center, open-label, prospective trial of perioperative blood pressure control for cardiac surgery. clevidipine was compared to nitroglycerine, sodium-nitroprusside and nicardipine in three parallel trials. The primary outcome was safety with a secondary outcome of efficacy.

Efficacy was measured by a method I have never seen before. The key measure of efficacy was keeping the blood pressure in the normal range so the authors measured the area under the curve for time versus SBP outside of the target blood pressure:

The authors found no difference in safety among the four drugs, though there was a pesky P=0.04 for increased death with sodium nitroprusside compared to clevidipine:

Clevidipine was significantly more efficacious than all competitors as individuals (except nicardipine) and when compared to all comparators.

Lupus Membranous Nephritis
Austin et al. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol (2009) vol. 20 (4) pp. 901-11

Prospective randomized controlled trial to compared cyclosporin for 11 months, to alternate-month cyclophosphamide for 11 months, to alternate-day prednisone alone.

Primary outcome was time to remission (less than 0.3 g of protein).Both CSA and prednisone were significantly better at achieving remission (complete and partial) than oral prednisone:
As we have seen in prior trials of cyclosporin in proteinuric renal disease (see FSGS), when the cyclosporin is stopped the proteinuria returns:
A well done, but small trial. Good to see an RCT in this rare entity because evidence based data on how to handle membranous lupus has been scant.

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Teaching on 2 Ell, the second week

On Monday one of our interns gave a lecture on the range of renal pathology possible found with lupus nephritis.

Lupus Nephritis

View SlideShare presentation or Upload your own. (tags: sle pathology)

This was a follow up on her lecture on the renal manifestations of lupus nephritis by WHO criteria. After her lecture we went down to bowels of the hospital to look at the kidney biopsy we had done on Friday on one of our patients with lupus.

On Thursday we began interpretation of Acid-Base disorders.
Also on Thursday I lectured the house staff on Nephrogenic Fibrosing Dermopathy, Acute Phosphate Nephropathy and Contrast Nephropathy. Renal adventures in imaging.

On Friday the 13th we completed Acid-Base disorders. As part of acid-base we talked about the anion gap. This article in CJASN on the anion gap was wonderful.