EDEMA BEYOND PROTEINURIA: CLINICOPATHOLOGIC CORRELATES AND HISTOPATHOLOGIC SPECTRUM OF LUPUS NEPHRITIS WITH NEPHROTIC AND NON-NEPHROTIC RANGE PROTEINURIA

 

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https://storage.unitedwebnetwork.com/files/1099/e3ead554cc5d7014605bd39648a5c5e3.pdf
EDEMA BEYOND PROTEINURIA: CLINICOPATHOLOGIC CORRELATES AND HISTOPATHOLOGIC SPECTRUM OF LUPUS NEPHRITIS WITH NEPHROTIC AND NON-NEPHROTIC RANGE PROTEINURIA

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Gigih Rahmandanu
Poernomo
Gigih Rahmandanu Poernomo dr.gigih@gmail,com Diponegoro University, Kariadi Hospital Internal Medicine, Division of Nephrology and Hypertension Semarang Indonesia *
Lestariningsih Lestariningsih lestariningsihwahyu@yahoo.com Diponegoro University, Kariadi Hospital Internal Medicine, Division of Nephrology and Hypertension Semarang Indonesia -
Ayudyah Nurani ayudyahnurani@gmail.com Diponegoro University, Kariadi Hospital Internal Medicine, Division of Nephrology and Hypertension Semarang Indonesia -
Arwedi Arwanto arwanto54@gmail.com Diponegoro University, Kariadi Hospital Internal Medicine, Division of Nephrology and Hypertension Semarang Indonesia -
Shofa Chasani shofachasani@gmail.com Diponegoro University, Kariadi Hospital Internal Medicine, Division of Nephrology and Hypertension Semarang Indonesia -
Ika Pawitra Miranti ika_pawitra@yahoo.com Diponegoro University, Kariadi Hospital Anatomical Pathology Semarang Indonesia -
Dwi Lestari Partiningrum dwilestari2005@yahoo.com Diponegoro University, Kariadi Hospital Internal Medicine, Division of Nephrology and Hypertension Semarang Indonesia -
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Lupus nephritis (LN) represents a major cause of morbidity in systemic lupus erythematosus, characterized by immune complex–mediated glomerular inflammation leading to diverse clinical presentations ranging from asymptomatic urinary findings to full nephrotic syndrome. Traditionally, edema has been attributed primarily to nephrotic-range proteinuria; however, emerging evidence indicates that hemodynamic, immunologic, and structural renal factors may also contribute to fluid retention even in non-nephrotic states. Understanding these clinicopathologic interrelations is crucial for improving prognostic assessment and management. This study aimed to evaluate demographic, clinical, laboratory, and histopathologic correlations of LN in patients with nephrotic and non-nephrotic proteinuria at a tertiary referral center.

A cross-sectional study was conducted on biopsy-proven LN patients at Dr. Kariadi General Hospital, Semarang, Indonesia, from August 2021 to August 2025. Demographic and clinical data, laboratory parameters, and kidney biopsy findings were analyzed. LN was classified according to the ISN/RPS 2003 criteria. Histologic activity and chronicity indices were assessed. Group comparisons were made using the Mann–Whitney test; correlations were examined using Spearman’s method. Linear regression analyses were performed with adjustment for histologic class (proliferative vs non-proliferative) and nephrotic status (nephrotic vs non-nephrotic range).

Forty-two patients were included (mean age 35.83 ± 11.34 years; 90.5% female). Most (66.7%) had non-nephrotic range proteinuria. Class IV LN was most frequent (35.7%), followed by Class III (28.6%), Class II (19.0%), Class V (11.9%), and Class I (4.8%). Proliferative classes (III–IV) comprised 64.3% of all biopsies. The mean activity and chronicity indices were 3.95 ± 3.04 and 2.07 ± 1.88, respectively. Significant histologic differences were found across classes for both indices: activity (p = 0.002) rose progressively from Class I to IV, with the highest median value in Class IV non-nephrotic (8.00); chronicity (p = 0.040) peaked in Class I for both nephrotic (4.00) and non-nephrotic (5.00) subgroups. MAP correlated positively with anti-dsDNA (r = 0.420, p = 0.006) and chronicity index (r = 0.380, p = 0.013), indicating interaction between systemic hemodynamics and renal chronicity. No significant correlation was found between urinary protein and anti-dsDNA, serum albumin, eGFR, or histologic indices. After adjustment for histologic class and nephrotic status, MAP remained significantly associated with anti-dsDNA (β = 0.368–0.401, p < 0.05) and chronicity (β = 0.449–0.462, p < 0.01).

In lupus nephritis with edema, the presence of fluid retention and disease severity are not solely explained by the degree of proteinuria. The significant and consistent association of MAP with anti-dsDNA and chronicity index—independent of histologic class and nephrotic status—demonstrates the multifactorial pathophysiology of LN, in which histopathologic features, systemic immune activity, and hemodynamic parameters jointly shape the clinical presentation. These findings underscore the importance of integrated clinicopathologic and hemodynamic evaluation in managing patients with lupus nephritis.

Kewords