What tests are used to diagnose lupus nephritis?

From the Guidelines

Lupus nephritis diagnosis involves a combination of clinical, urinary, and laboratory parameters, with kidney biopsy being the gold standard for confirmation.

Diagnostic Tests

• Kidney biopsy: considered the most accurate method for diagnosing lupus nephritis, as it allows for the assessment of activity and chronicity features that inform treatment decisions and prognosis 1
• Urinary parameters:
  • Proteinuria: a level of 500 mg/d is suggested as a threshold for further investigations, but the severity of proteinuria can vary considerably in severe active nephritis 1
  • Glomerular hematuria and/or cellular casts: can be an indication for renal biopsy 1
• Laboratory parameters:
  • Serum creatinine and eGFR: to assess renal function 1
  • Serum anti-dsDNA antibody levels: to assess disease activity 1
  • Serum C3 and C4: to assess disease activity 1
  • Complete blood cell count: to assess for potential complications 1

Approach to Diagnosis

A holistic assessment including clinical, urinary, and laboratory parameters, and repeated investigations to note the progression of abnormal findings over time, are important in informing clinical management decisions 1. The International Society of Nephrology (ISN)/Renal Pathology Society (RPS) scheme is recommended for classifying kidney biopsy findings 1. Electron microscopy can be helpful in ascertaining ultrastructural details of histopathology, such as the extent and severity of podocyte injury and the location of immune deposits 1.

From the Research

Diagnostic Tests for Lupus Nephritis

The diagnosis of lupus nephritis (LN) involves several tests, including:

• Urinalysis, which is a useful screening test for LN 2
• Quantification of proteinuria, which can be performed with either a urine protein-to-creatinine ratio or 24-h urine sample collection for protein 2
• Renal biopsy, which remains the gold standard for diagnosis of LN 2, 3, 4
• Serum biomarkers, such as anti-double-stranded DNA antibodies and complement components 3 and 4, which are used to monitor SLE and LN disease activity and flares 2
• Nonconventional biomarkers, such as anti-C1q and surrogate markers of type 1 interferon regulatory genes (INF gene signature), which have been found to correlate with LN 2
• Urinary biomarkers, such as monocyte chemoattractant protein 1, neutrophil gelatinase-associated lipocalin, tumor necrosis factor-like inducer of apoptosis, and vascular cell adhesion molecule 1, which have been identified as potential biomarkers for LN 2, 3
• Estimated glomerular filtration rate (eGFR) or proteinuria testing, which are used to monitor renal function in LN patients 5

Pathologic Features of Lupus Nephritis

The diagnosis of LN can also be made based on pathologic features, including:

• "Full-house" staining by immunofluorescence
• Intense C1q staining
• Extraglomerular deposits
• Combined subendothelial and subepithelial deposits
• Endothelial tubuloreticular inclusions These features can distinguish LN from nonlupus glomerulopathies with high specificity and varying sensitivity 6