Proteinuria Recovery Heads Off LN Comorbidities

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WASHINGTON, D.C.—Achieving partial or complete recovery from proteinuria in patients with active lupus nephritis (LN) at one year from disease onset may protect against comorbidities, including end-stage kidney disease, according to a new study presented at the American College of Rheumatology annual meeting.

“Proteinuria recovery at one year is a predictive factor for long-term outcomes—renal failure, accrual of severe damage and death—in lupus nephritis patients,” said lead investigator Zahi Touma, MD, PhD, a postdoctoral clinical research fellow of rheumatology at the University of Toronto Lupus Clinic. “Although complete recovery of proteinuria is ideal and protects against the development of long-term outcomes, even partial recovery may be protective.”

The vast majority of therapeutic trials have used complete proteinuria recovery as the primary endpoint, Dr. Touma said. It is theorized, however, achieving a 50% or greater decrease in proteinuria from baseline may improve long-term outcomes.

Dr. Touma and his colleagues studied 196 active LN patients registered at a large lupus clinic. The group was 84% female. Forty-seven (24%) patients achieved partial proteinuria and 52 (26.5%) had a complete proteinuria recovery. The researchers defined complete proteinuria recovery as proteinuria less than 0.5 g/24 hours and partial response as a 50% or greater decrease in the level of proteinuria from baseline. Patients were defined as “not recovered” if they had less than 50% recovery. For this investigation, proteinuria recovery was identified if it was present on two consecutive visits within one year.

The researchers analyzed the following long-term outcomes: death, estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m2 or less, initiation of dialysis or receipt of a kidney transplant, Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) greater than greater than 3 and atherosclerotic events.

The following long term outcomes were observed after an approximate mean time of 4 years from study start. 11% of patients developed an eGFR of 15 or less and 8% started dialysis or underwent kidney transplantation. In addition 11% of patients died, 4% developed atherosclerotic events and 21% experienced damage (SDI greater than 3).

Patients achieving a complete proteinuria response at one year had a 79% decreased likelihood of having an eGFR of 15 or less within at least 6 years of follow-up. Patients achieving partial proteinuria recovery had a trend for being protected from developing an eGFR of 15 or less but this was not statistically significant. The complete responders also had 80% decreased likelihood of an SDI greater than 3. No patient with complete proteinuria recovery achieved at one year went on to dialysis or renal transplantation and no atherosclerotic events have occurred within at least six years of follow-up.

“Physicians should aim to achieve a complete proteinuria recovery in lupus nephritis patients. Nevertheless, complete recovery is slow,” Dr. Touma told Renal & Urology News. “Physicians should also measure partial proteinuria recovery especially since 43% of the patients with partial proteinuria recovery at one year will achieve complete recovery at two years.”

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