Introduction:
Current guidelines for managing lupus nephritis (LN) emphasize proteinuria. A kidney biopsy (KB) is recommended for patients with persistent proteinuria (urinary protein-to-creatinine ratio exceeding 500 mg/g), regardless of urinary sediment abnormalities, such as dysmorphic red blood cells (RBCs). Proteinuria can reflect various LN conditions, including active inflammation, proliferative lesions, or membranous nephropathy, but may also result from chronic kidney damage or scarring. After an initial diagnosis, repeat biopsies may be necessary, as clinical markers like proteinuria do not always correspond with histological changes. This study aimed to assess the association between increasing proteinuria from the first to the second KB and changes in histopathological LN classification, as well as the appearance of hematuria.
Methods:
We conducted a retrospective analysis of LN patients who had multiple KBs between 2000 and 2021. Nephrologists with expertise in kidney pathology analyzed the biopsy samples using light microscopy and immunofluorescence. For patients with more than two biopsies, only the first and second were included. Biopsy results were classified or reclassified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) system for LN. Statistical analysis was performed using SPSS®, with significance set at p ≤ 0.05. Patients were divided into two groups: those with and those without LN class changes. A subanalysis was also performed on patients who transitioned to a more proliferative class (e.g., from class III to IV, or from any class to class III or IV). An increase in proteinuria was defined as a 0.1 g rise in 24-hour urine or the protein/creatinine ratio.
Results:
Proteinuria data from both biopsies were available for 41 patients, and hematuria data for 43. Proteinuria increased in 11 out of 41 patients (26.8%), but no statistically significant correlation was found with LN class changes (p = 0.151) or progression to a more proliferative class (p = 0.566). However, nephrotic-range proteinuria was associated with higher chronicity scores (2.54 ± 2.96 vs. 2.42 ± 2.88, p = .003). Hematuria was observed in only 3 patients, with no significant association with class changes (p = 0.545) or progression to a more proliferative class (p = 0.370).
Conclusions:
In conclusion, although an increase in proteinuria was noted in a subset of patients, it was not a reliable predictor of LN class changes or progression to more proliferative forms. Nephrotic-range proteinuria was linked to higher chronicity scores, suggesting its association with chronic kidney damage. Hematuria, though present in a small number of patients, showed no significant correlation with LN class changes. However, due to the limited sample size, further research with larger cohorts is needed to better understand the role of hematuria in LN progression. Given the complex relationship between clinical markers and histological changes, repeat kidney biopsies remain essential for guiding treatment and monitoring disease progression in LN.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.