Published online Jun 20, 2026. doi: 10.5493/wjem.v16.i2.119440
Revised: March 29, 2026
Accepted: April 15, 2026
Published online: June 20, 2026
Processing time: 136 Days and 1.9 Hours
Lupus nephritis (LN) is a significant cause of kidney morbidity in patients with systemic lupus erythematosus. While glomerular lesions are the primary focus of current classifications, tubulointerstitial involvement may significantly influence renal outcomes. There is limited data on tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) in Middle Eastern populations.
To examine the clinical, pathological, and prognostic significance of coexisting TII and TID in patients with biopsy-proven LN from Saudi Arabia.
We retrospectively analyzed 100 patients with biopsy-confirmed LN. Patients were stratified into those with TII + TID (n = 48) and those without (n = 52). Baseline demographics, clinical features, laboratory and immunological data, and histopathological findings, including modified National Institutes of Health (NIH) activity and chronicity scores, were collected. Multivariable logistic regression identified predictors of TII + TID. Renal response during follow-up was evaluated using Kaplan-Meier analysis, and predictors of adverse composite outcomes were assessed using Cox regression.
Patients with TII + TID had lower baseline estimated glomerular filtration rate (77.7 ± 37.4 mL/minute/1.73 m2 vs 98.2 ± 52.7 mL/minute/1.73 m2; P = 0.028) and higher low-density lipoprotein cholesterol (LDL-C; 3.01 ± 1.88 mmol/L vs 1.78 ± 1.82 mmol/L; P = 0.006). They also had higher modified NIH activity (6.17 ± 3.90 vs 3.13 ± 3.18; P < 0.001) and chronicity scores (4.21 ± 1.74 vs 1.85 ± 2.44; P < 0.001). Proliferative classes, especially class III (35.4% vs 15.4%) and class IV + V (20.8% vs 15.4%; P = 0.024), were more common in this group. Independent predictors of TII + TID included class III (OR = 150.42; P = 0.006), class IV + V (OR = 44.11; P = 0.03), LDL-C (OR = 2.26; P = 0.004), fibrinoid necrosis [Exp(B) = 2.29; P = 0.041], and interstitial inflammation [Exp(B) = 73.29; P < 0.001]. Patients with TII + TID had slower and reduced rates of achieving renal remission. Higher baseline serum creatinine, older age, elevated C-reactive protein (CRP), and the presence of hyaline deposits were associated with worse composite renal outcomes. In contrast, total glomerulosclerosis showed an inverse association in the subgroup but not in the overall cohort.
TII and damage are common in LN and are closely associated with proliferative glomerular lesions, fibrinoid necrosis, and adverse renal outcomes. The presence of TII + TID, along with baseline creatinine, CRP, and hyaline deposits, identifies patients at higher risk for poor renal prognosis. These findings highlight the importance of evaluating the tubulointerstitial compartment for risk stratification and tailored management in LN, particularly in the Saudi Arabian population.
Core Tip: Although current lupus nephritis (LN) classifications focus mainly on glomerular lesions, tubulointerstitial involvement is frequent and clinically relevant. In this Saudi cohort, the presence of combined tubulointerstitial inflammation and damage was associated with proliferative disease, higher activity and chronicity scores, and poorer renal outcomes. These patients achieved remission more slowly and less often during follow-up. Baseline kidney function, systemic inflammation, and selected histologic features further influenced prognosis. Detailed assessment of the tubulointerstitial compartment may therefore add meaningful prognostic information in LN.