The histologic class of lupus nephritis (LN) was not predicted by proteinuria levels, while a strong prediction of progression to chronic kidney disease (CKD) was observed with an estimated glomerular filtration rate (eGFR) cutoff of 75 mL/min/1.73 m2 after 1 year of treatment, according to study results published in Rheumatology (Oxford)
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that often impacts the kidneys, with LN occurring among approximately half of these patients. Despite improved survival rates, LN remains linked to end stage renal disease and mortality, especially in cases of proliferative LN (PLN) and membranous LN (MLN), necessitating further multicenter studies to validate long-term outcomes.
In a multicenter observational study, researchers conducted a retrospective analysis of data from the nationwide Rheumatic Disease Portuguese Registry. Their objective was to analyze PLN and MLN in terms of clinical and laboratory manifestations, long-term outcomes, and to identify predictors of progression to CKD.
Patients who met the American College of Rheumatology 1997 or Systemic Lupus International Collaborating Clinics 2012 criteria for SLE with a confirmed renal biopsy that showed LN class were eligible for inclusion.
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A repeated renal biopsy may be useful to help distinguish between ongoing active disease (needing more aggressive immunosuppression) from irreversible damage.
Patients were categorized into 3 distinct groups based on the classification of their initial renal biopsy:
Renal response was categorized as complete, partial, or no response based on proteinuria levels and eGFR, while CKD was defined as decreased GFR below 60 mL/min/1.73 m2 for at least 3 months. Researchers also collected various demographic and clinical data.
A total of 260 patients with biopsy-confirmed LN were included in the final analysis, over a median follow-up period of 8 years. Of these, 203 patients had PLN, 47 had MLN, and 10 had mixed LN. At the time of the renal biopsy the median patient age was 30 years and on average, it took 1 year from the diagnosis of SLE to the development of LN.
Patients with MLN exhibited significantly lower serum creatinine levels (0.70 mg/dL) vs those with PLN (0.80 mg/dL; P =.003), while proteinuria levels were similar across both groups (P =.641).
Among patients with PLN, complement levels were decreased, while levels were nearly normal among individuals with MLN. Patients with MLN vs PLN also had fewer instances of positive antidouble-stranded DNA antibodies (48% vs 92%; P <.001).
After 1 year, 62% of patients had achieved a complete renal response, with an additional 5% achieving a partial response.
A lower level of proteinuria at the time of diagnosis was correlated with an increased likelihood of achieving a complete renal response. Conversely, an eGFR of 75 mL/min/1.73 m2 or lower at 1 year strongly predicted progression to CKD (hazard ratio, 22.86; 95% CI, 8.38- 62.36; P <.001). Other factors that could potentially predict CKD progression included the use of azathioprine, older age at diagnosis, and male sex.
Throughout the follow-up period, 6% of patients (n=16/260) died, mainly from infection (n=6) and cancer (n=3). The cumulative survival rates for patients across 5, 10, 15, and 20 years reached 97%, 93%, 91%, and 88%, respectively.
Study limitations include the small sample size and the use of combined retrospective and prospective data.
“A repeated renal biopsy may be useful to help distinguish between ongoing active disease (needing more aggressive immunosuppression) from irreversible damage,” the researchers stated. “All patients should be closely monitored to ensure that any flares are rapidly detected and treated, in order to avoid further loss of GFR,” they concluded.