Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE), occurring in approximately 60% of adults, and is associated with a high degree of morbidity and mortality (1). Currently, the evaluation of kidney involvement in patients with SLE is based on a proteinuria-centric approach. Most guidelines recommend a kidney biopsy for a urine protein-to-creatinine ratio (UPCR) ≥500 mg/g. However, some studies have reported significant inflammatory LN in patients with SLE and even low-grade proteinuria below this threshold (2–5). In a cohort of patients with SLE and isolated proteinuria <1000 mg/g, without active urinary sediment (hematuria), 60% (52 of 87) had histologic evidence of active LN (2). The optimal threshold of proteinuria for early detection of LN remains unclear.
In a recent study in CJASN, Wang et al. (6) aimed to evaluate the progression of low-grade UPCR (between 200 and 500 mg/g) to clinically relevant proteinuria. In this observational study of 151 patients with SLE and low-grade proteinuria, 50% (76 of 151) progressed to UPCR >500 mg/g within a short median time of 1.2 years; 61% (46 of 76) were “fast progressors” who reached this state within 2 years of developing low-grade proteinuria. Among the 20 clinically indicated kidney biopsies during the initial 2 years, 80% (16 of 20) showed active LN with subsequent changes in treatment plans.
Risk factors associated with the progression of proteinuria within 2 years of follow-up included low complement levels and a shorter duration of SLE at the index date. Other associated factors included hypertension, diabetes mellitus, younger age, and hematuria.
Complement activation, noted by a decrease in circulating C3 and C4 levels, has long been viewed as an indicator of active LN. In this study, low complement levels had a high sensitivity (82%) and negative predictive value (94%) for progression to overt proteinuria. Monitoring the trend of serum complement levels can be valuable in evaluating patients with SLE and low-grade proteinuria to aid in the early detection of active LN.
The results of this study may warrant a change to our current approach to low-grade proteinuria in SLE. Careful monitoring of urinary sediment and serum complement levels can aid in the early detection of LN and subsequent interventions that reduce long-term complications. Future studies to better understand the underlying pathways of injury and determine biomarkers of early disease are eagerly awaited.
References
- 1.↑
Mok CC, et al. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheum 2013; 65:2154–2160. doi: 10.1002/art.38006
- 2.↑
Chedid A, et al. Low-level proteinuria in systemic lupus erythematosus. Kidney Int Rep 2020; 5:2333–2340. doi: 10.1016/j.ekir.2020.09.007
- 3.
Hsieh YP, et al. The value of early renal biopsy in systemic lupus erythematosus patients presenting with renal involvement. Clin Nephrol 2012; 77:18–24. doi: 10.5414/cn107094
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Zabaleta-Lanz M, et al. Silent nephritis in systemic lupus erythematosus. Lupus 2003; 12:26–30. doi: 10.1191/0961203303lu259oa
- 5.↑
De Rosa M, et al. Low-grade proteinuria does not exclude significant kidney injury in lupus nephritis. Kidney Int Rep 2020; 5:1066–1068. doi: 10.1016/j.ekir.2020.04.005
- 6.↑
Wang S, et al. Short- and long-term progression of kidney involvement in systemic lupus erythematosus patients with low-grade proteinuria. Clin J Am Soc Nephrol 2022; 17:1150–1158. doi: 10.2215/CJN.01280122
