The key points of lupus nephritis treatment

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement, strong clinical heterogeneity, and complex pathogenesis. Genetic susceptibility and environmental factors are closely related to the onset of SLE. Lupus nephritis (LN) is a type of glomerulonephritis and is considered to be one of the most serious organ manifestations of SLE. Most SLE patients may develop LN within 5 years of diagnosis, and about 10% of LN patients will develop end-stage renal disease. LN is an important cause of morbidity and mortality in SLE patients. Early accurate diagnosis and timely treatment are crucial to improving the prognosis of SLE patients.

At what stage of SLE progression should LN be suspected? In patients with SLE, LN should be considered if urine sediment microscopy shows active findings of persistent hematuria and/or cellular casts, proteinuria, and/or elevated serum creatinine (or decreased estimated glomerular filtration rate). High titers of anti-dsDNA antibodies and low complement (C3 and C4) levels often indicate active SLE, especially LN, but the usefulness of serologic evaluation varies from person to person.

SLE patients can be diagnosed with LN when they have the following clinical and laboratory abnormalities, including:

(1) Proteinuria persists at >0.5 g/24 h, or urine protein is 3+ on a random urine test, or the urine protein/creatinine ratio is >500 mg/g (50 mg/mmol).

(2) Microscopic examination of urine sediment reveals cellular casts, including red blood cell casts, hemoglobin casts, granular casts, tubular casts, or mixed casts.

(3) Active urine sediment (excluding urinary tract infection, urine white blood cells >5/HPF, urine red blood cells >5/HPF), or the presence of red blood cell casts and/or white blood cell casts.

Pathogenesis and clinical manifestations of LN

SLE is mainly caused by the deposition of immune complexes caused by numerous antibodies produced by B cells. The deposition of immune complexes in the glomeruli is the direct cause of LN. A small part of it damages the kidneys through non-immune complex pathways such as lupus interstitial nephritis and renal vascular disease. The clinical manifestations of LN are mainly hematuria, proteinuria, acute or chronic renal failure and hypertension.

Renal biopsy and specific markers are reliable diagnostic methods for LN. Renal biopsy is currently the most effective and reliable diagnostic method for LN.

(1) Renal biopsy: The 2012 American College of Rheumatology guidelines for the screening, treatment, and management of lupus nephritis stipulate that a renal biopsy showing immune complex glomerulonephritis consistent with LN pathology is the most reliable criterion for diagnosing LN. Subsequently, the 2019 European League Against Rheumatism guidelines and the 2021 Improving Global Kidney Outcomes guidelines further emphasized the importance and irreplaceability of renal biopsy.

Renal biopsy pathology shows that the kidneys are almost 100% involved, and the pathological damage mainly involves the glomeruli, tubulointerstitium, and blood vessels. The pathological classification of renal biopsy is generally divided into 6 types, among which the most common are types III to V, namely focal LN, diffuse LN, and membranous LN. LN has a linear relationship with the damage to renal function during the active stage, and has a greater impact on renal function; during the remission period, the damage to renal function is relatively stable. Therefore, LN needs to be treated in time during the active stage to prevent further damage to renal function.

(2) Markers: Although renal biopsy is a reliable diagnostic standard for LN, its risks cannot be ignored. Non-invasive marker diagnosis represented by soluble inflammatory mediators and urine biomarkers has opened up new ideas for the accurate diagnosis of LN, such as vascular cell adhesion molecule-1, activated leukocyte adhesion molecule, plasma interleukin-17 and interleukin-23, platelet factor 4 and other urine protein markers.

The progress in the treatment of LN is mainly targeted therapy for B cells

(1) Targeted therapy of B cells: The treatment of LN is based on the histological classification of the kidneys, with the goal of reducing the patient's proteinuria, preventing or delaying the deterioration of renal function, and reducing morbidity and mortality. The current progress in the treatment of LN is mainly targeted therapy for B cells. In recent years, drugs commonly used in clinical treatment include belimumab, tetasipu, rituximab, and obinutuzumab. Belimumab mainly blocks or inhibits lymphocytes and factors, tetasipu mainly blocks lymphocyte hyperplasia, and rituximab and obinutuzumab mainly target CD20 expressed by B cells, which can play a therapeutic role.

(2) Innovative treatments: In addition to B cell targeted therapy, there are some innovative treatment strategies for LN, such as therapy targeting T lymphocytes, therapy targeting co-stimulatory pathways, therapy targeting proinflammatory cytokines, and therapy targeting the complement system, which are currently in the stage of continuous exploration.

References

[1] Dong Yaqian, Lu Xianyuan, Tang Lan, et al. Research progress on the pathogenesis, biomarkers and treatment status of lupus nephritis[J]. Journal of Practical Medicine, 2018, 34(10): 1605-1609.

[2] Sun Lingyun, Liu Yudong. New progress in the diagnosis and treatment of lupus nephritis[J]. Chinese Journal of Clinical Immunology and Allergy, 2022, 16(05):545-547.