People with lupus nephritis who have nephrotic syndrome — loss of protein in urine, low albumin levels in circulation, elevated lipid levels, and swelling — are less likely to have a kidney response over one year, a review study of two clinical trials shows.
It also stresses that more clinical studies and outcome predictors are needed to assess the effects of new therapies and understand better the prognosis of people with lupus nephritis who have nephrotic syndrome.
The study, “Outcome of participants with nephrotic syndrome in combined clinical trials of lupus nephritis,” was published in the journal Lupus Science and Medicine.
Nephrotic syndrome is a common manifestation of kidney disease characterized by high levels of protein in urine (proteinuria), low serum albumin, high levels of cholesterol or triglycerides in blood (hyperlipidemia), and swelling.
It may result in serious complications including infections, high blood pressure, and abnormal blood coagulation.
Many patients — reportedly 30% to 70% — with lupus nephritis, which is an inflammation of the kidneys caused by lupus, also have nephrotic syndrome.
The syndrome “as initial disease presentation or as a disease flare, has important prognostic implications for treatment outcomes in lupus nephritis,” researchers wrote.
In some studies, nephrotic syndrome has been associated with a poorer prognosis and a lower probability of achieving a kidney response in lupus nephritis patients.
Despite the negative effect among these patients, no major trial has specifically analyzed how the syndrome affects the outcomes of lupus nephritis patients.
A team of U.S. and U.K. researchers, including representatives at Genentech, sought to determine if nephrotic syndrome lowered the chances of lupus nephritis patients of achieving a kidney response over one year of observation.
With that purpose, researchers reviewed data from two large randomized controlled trials testing the effectiveness of Rituxan (rituximab) and Ocrevus (ocrelizumab) in lupus nephritis — LUNAR (NCT00282347) and BELONG (NCT00626197).
Creatinine is a body waste removed by the kidneys, leaving the body through urine. High creatinine levels may be a sign of poor kidney function. The UPCR ratio is also used to see if kidneys are working normally as excess protein leaking into urine may also be a sign of kidney disease.
The combined analysis of both trials revealed that nephrotic syndrome significantly reduced the chances of patients with lupus nephritis to reach a positive kidney response over one year.
Of the 157 subjects with nephrotic syndrome at study start, only 26% achieved a kidney response after one year of follow-up. In comparison, more than half (52.5%) of those without nephrotic syndrome had an improvement in kidney function over the same period.
In spite of this difference, most patients with nephrotic syndrome had clinically important improvements during their time in the trials.
For example, they had stronger decreases in excess protein in urine compared with non-nephrotic subjects. In addition, a majority of them (80%) achieved resolution of their nephrotic syndrome in a median time of 16 weeks.
All nephrotic responders had more than 50% reduction in proteinuria after six months, supporting the hypothesis that a “reduction in proteinuria in the first 6 months of treatment could be a predictor of long-term renal outcomes for nephrotic syndrome participants.” researchers said.
It also suggests that longer trials may be better to assess responses in subjects with nephrotic syndrome.
These patients may require more time to reach low protein levels in urine, thus longer trials — of one-and-a-half or two years — would be better to assess the effect of new therapeutic approaches in this group of patients.
Researchers stress that more studies “are necessary to better understand the overall prognosis” of patients with nephrotic syndrome and to evaluate more goals for use in future lupus nephritis trials.
Future studies should analyze the response of these patients separately, they added.