Low-Level Proteinuria in Systemic Lupus Erythematosus

Abstract

Introduction: In patients with systemic lupus erythematosus (SLE) without concurrent active urinary sediment or unexplained acute kidney injury (AKI), current guidelines recommend performing a kidney biopsy in those with at least 500 mg/24-hour (European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association [EULAR/ERA-EDTA]) or 1000 mg/24-hour (American College of Rheumatology [ACR]) proteinuria. To evaluate the relevance of these indications, we studied histopathologic findings in patients with SLE with proteinuria below these cutoffs. Methods: We retrospectively reviewed the clinical, laboratory and histological characteristics of patients with SLE with <1000 mg/24-hour proteinuria (or mg/g urinary protein-to-creatinine ratio [UPCR]) who underwent their first kidney biopsy between 2003 and 2018. Results: We identified 87 patients with SLE with proteinuria less than 1000 mg/24-hour (or mg/g UPCR); 52 of 87 (60%) with isolated proteinuria, that is, without AKI or active urinary sediment (hematuria). Histologic evidence of lupus nephritis (LN) was present in 40 of 52 (76%). Of the 40 patients with LN, 12 had class I or II, 14 had class III or IV, 8 had class V, 6 had a combined proliferative and membranous LN. Non-lupus diagnoses included focal segmental glomerulosclerosis, acute interstitial nephritis, and others. Patient's age, low C3, low C4, and positivity for anti-double-stranded DNA (anti-dsDNA) antibodies predicted the histological diagnosis of LN on univariate logistic regression; however, a multivariate model including these parameters as independent covariates failed to predict LN. Conclusions: Patients with SLE with low-level proteinuria may have significant lupus-or non-lupus-related kidney disease with management implications. There was a significant burden of severe forms of LN. The presence of LN was not predicted by laboratory abnormalities. Based on our findings, we suggest current guidelines be revised to expand kidney biopsy indications to include isolated proteinuria of any grade.

Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria

“…Laboratory and urine WBC (k/ml), median (IQR) kidney injury (class III, IV, or V) on biopsy (9,10,(22)(23)(24)(25). This study confirms that over half of patients with SLE and low-grade proteinuria progress to overt proteinuria, supporting the role for early biopsy to diagnose lupus nephritis, even in the absence of hematuria.…”

Association between Red Cell Distribution Width to Platelet Ratio and Disease Activity among Iraqi Patients with Systemic Lupus Erythematosus

“…According to Chedid et al, 60% of patients exhibited isolated low-level proteinuria coupled with acute renal damage and hematuria. This can be explained by the fact that 76% of patients had histological evidence of lupus nephritis [26]. In this investigation, the mean platelet count in SLE patients was considerably lower than in controls.…”

Urinary HER2, TWEAK and VCAM-1 levels are associated with new-onset proteinuria in paediatric lupus nephritis

“…The data thus far indicate an association of the biomarkers in the urine with different measures of disease activity. The biomarkers were most strongly associated with new proteinuria which could be a marker of new renal insult 31 32. We leveraged the longitudinal nature of our study to examine whether the time point prior to the rise in R-SLEDAI, serum creatinine or new-onset proteinuria demonstrated higher levels of biomarkers compared with biomarker levels in those who never flared or time points without flare (figure 4).…”