Forgotten compartment: Impact of tubulointerstitial inflammation and damage on renal outcomes in lupus nephritis from Saudi Arabia.

BACKGROUND

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.

AIM: To examine the clinical, pathological, and prognostic significance of coexisting TII and TID in patients with biopsy-proven LN from Saudi Arabia.

METHODS

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.

RESULTS

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.

CONCLUSION

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.