Clinical-Pathological Characteristics of Renal Injuries Identify Different Clusters in Patients With Antiphospholipid Antibodies

Savino Sciascia; Jinoos Yazdany; Gabriella Moroni; Jan Ulrich Becker; Surya V Seshan; Danieli Andrade; Giacomo Emmi; Maria J Cuadrado; Massimo Radin; Irene Cecchi; Emanuele De Simone; Antonella Barreca; Leonardo Caroti; Samantha Innocenti; Roberta Fenoglio; Dario Roccatello

doi:10.1016/j.ekir.2023.01.018

Clinical-Pathological Characteristics of Renal Injuries Identify Different Clusters in Patients With Antiphospholipid Antibodies

Kidney Int Rep. 2023 Jan 23;8(4):754-763. doi: 10.1016/j.ekir.2023.01.018. eCollection 2023 Apr.

Authors

Savino Sciascia¹, Jinoos Yazdany², Gabriella Moroni³, Jan Ulrich Becker⁴, Surya V Seshan⁵, Danieli Andrade⁶, Giacomo Emmi⁷, Maria J Cuadrado⁸, Massimo Radin¹, Irene Cecchi¹, Emanuele De Simone¹, Antonella Barreca⁸, Leonardo Caroti⁷, Samantha Innocenti⁷, Roberta Fenoglio¹, Dario Roccatello¹

Affiliations

¹ University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases, Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, Turin, Italy.
² Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
³ Department of Biomedical Sciences, IRCCS Humanitas Research Hospital, Rozzano, Lombardia, Italy.
⁴ Institute of Pathology, University Hospital Cologne, Cologne, Germany.
⁵ Department of Pathology and Laboratory Medicine, Weil Cornell Medicine, New York, New York, USA.
⁶ Rheumatology, University of Sao Paulo, Sao Paulo, Brazil.
⁷ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
⁸ Division of Pathology, Città della Salute e della Scienza Hospital, Turin, Italy.

Abstract

Introduction: Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS).

Methods: We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months.

Results: A total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles.

Conclusion: Three different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN).

Keywords: APS nephropathy; antiphospholipid antibodies; antiphospholipid syndrome; systemic lupus erythematosus; thrombosis; thrombotic microangiopathy.