Severe pulmonary arterial hypertension development despite lupus nephritis remission: association with podocytic infolding glomerulopathy

Abstract

Background: Pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) represents a significant complication with incompletely understood pathogenesis. Notably, podocytic infolding glomerulopathy (PIG), a rare pathological phenomenon in SLE-related renal lesions, has not been previously linked to PAH development. The cardiovascular safety profile of belimumab, a biologic agent for SLE treatment, requires continued surveillance, particularly regarding potential pulmonary vascular complications.

Case presentation: We report a 30-year-old male with SLE who unexpectedly developed severe PAH following complete remission of class V lupus nephritis. The patient’s renal pathology exhibited PIG features, initially overlooked at diagnosis. Despite rapid improvement in renal function with conventional immunosuppression, PAH persisted, suggesting the critical role of vascular remodeling in PAH perpetuation. Glucocorticoid therapy resulted in avascular necrosis of the femoral head. Notably, PAH emerged during belimumab treatment and showed remarkable improvement following belimumab discontinuation, raising important concerns about potential therapy-related cardiovascular complications. Pulmonary arterial pressure significantly decreased with marked symptomatic improvement.

Conclusion: This case underscores the necessity for clinical vigilance in SLE management.For patients with SLE-PIG, close monitoring for potential PAH development is essential, even after apparent SLE remission. Most critically, this case highlights potential cardiovascular safety signals associated with belimumab therapy, emphasizing the need for systematic monitoring of pulmonary vascular complications in patients receiving novel biologic treatments—an observation warranting urgent verification in future clinical investigations.

Clinical trial number: Not applicable.

Keywords: Belimumab; Cardiovascular monitoring; Case report; Drug safety; Lupus nephritis; Podocytic infolding glomerulopathy; Pulmonary arterial hypertension; Systemic lupus erythematosus.

Fig. 1

(a): HE staining shows an increase in the number of cells in the glomerulus (HE×400); (b): Periodic Acid-Schiff (PAS) staining reveals mesangial cell proliferation and matrix expansion (PAS×400); (c): Periodic Acid-Silver Methenamine (PASM) staining indicates glomerular basement membrane thickening and the presence of spike-like structures (PASM×400); (d): Immunofluorescence microscopy reveals glomerular deposition of C1q (IF×400); (e) and (f): Microtubules and microspheres can be seen in the thickened GBM, and podocytes are invaginated (e, EM ×20000; f, EM ×10000).The thickened Glomerular Basement Membrane (GBM) shows microtubules and microspheres, with podocyte foot process effacement evident

Fig. 2

Cardiac and radiological findings. (a) Cardiac Doppler showing tricuspid regurgitation with velocity 436.5 cm/s and pressure gradient 76.2 mmHg. (b) Follow-up Doppler showing reduced velocity (306.9 cm/s) and pressure gradient (37.7 mmHg). (c, d) Pulmonary artery CTA demonstrating dilated pulmonary trunk (36 mm) with enlarged right (26.53 mm) and left (26.78 mm) pulmonary arteries. (e, f) Hip MRI showing bilateral femoral head deformation with flattened surfaces and irregular contours (arrows): low, uneven signals on T1-weighted imaging (e) and predominantly high signals on T2-weighted imaging (f)