Vitamin D
Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.
In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).
“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
Mycophenolate mofetil
The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.
Left untreated, he would be in end-stage renal disease within a year, she said.
“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.
This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.
“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”
In this case, however, the best induction therapy is mycophenolate mofetil, she said.
“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”
In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.
After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”
“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.
“So we really need something that’s much more successful.”
Steroids
How much prednisone should lupus nephritis patients get?
As little as possible, according to Dr. Petri.
“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”
She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.
“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.
“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.
EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”
“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”
Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).
“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”
Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.
“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.
“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).
Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).
Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.