Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Key Points Kidney pathology in scleroderma renal crisis was heterogeneous, with three histologic patterns of kidney injury identified by hierarchical cluster analysis. Creatinine, acute arteriolar thrombotic microangiopathy, and onion skinning in small arteries were associated with a higher risk of kidney failure. Complement system was activated in these injured vessels. Background Scleroderma renal crisis (SRC) is a severe complication of systemic sclerosis that is associated with higher morbidity and mortality. However, limited data are currently available regarding the factors affecting kidney outcome during SRC. The objective of this study was to describe kidney histopathology in SRC and to evaluate its association with kidney failure. Methods We performed a French multicenter retrospective study that included 65 patients who underwent a kidney biopsy in the context of SRC between 2006 and 2020. Nonsupervised hierarchical cluster analysis was used to identify histologic patterns. Cox model was performed to estimate the hazard ratios associated with histologic parameters for kidney failure, defined as the need for long-term dialysis therapy or eGFR <15 ml/min per 1.73 m 2 at the last follow-up. Multiplexed sequential immunofluorescence and proximity ligation assay was used in kidney biopsies to analyze complement system activation. Results Kidney pathology in SRC was more heterogeneous than expected, with three histologic patterns of kidney injury identified by cluster analysis. Multivariable analysis showed that together with creatinine at presentation, acute arteriolar thrombotic microangiopathy and onion skinning in small arteries were independently associated with the risk of kidney failure. Multiplex immunofluorescence identified fractions from the complement classical pathway in arterioles and arteries in SRC, while proximity ligation experiments confirmed the in situ activation of classical pathway C3 convertase. Complement terminal pathway fraction C5b-9 was localized in injured arteries. Conclusions This study shows that the clinical definition of SRC encompasses heterogeneity in the patterns of kidney injury. Acute arteriolar thrombotic microangiopathy and onion skinning were associated with kidney failure. Complement system was activated in these injured vessels.

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Journal
Journal of the American Society of Nephrology
Published
2025-05-07
DOI
https://doi.org/10.1681/asn.0000000720
Citations
3
Primary Topic
Systemic Sclerosis and Related Diseases
Type
article
Field-Weighted Citation Impact
4.41
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article

Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Rafik Mesbah, Alexis Mathian, Christian Gosset, Luc Mouthon et al.
3 citations
Journal of the American Society of Nephrology
Systemic Sclerosis and Related Diseases
4.41
article

Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Rafik Mesbah, Alexis Mathian, Christian Gosset, Luc Mouthon, Olivier Aubert, Marie Frimat, Emmanuel Estève, Noémie Jourde‐Chiche, Idris Boudhabhay, Pierre Isnard, Alexandre Karras, Viviane Gnemmi, Jean-Paul Duong-Van-Huyen, Aurélie Hummel, Sophie Chauvet, P Housset, Lubka T. Roumenina, Yannick Binois, Benjamin Chaigne, Marion Rabant, Anne Lyse Langlois, David Buob, Isabelle Brochériou, Olivier Moranne, Laurent Daniel, Marie-Sophie Meuleman, Éric Thervet, T. Quéméneur, Sébastien Rivière
article en
3 citations

Abstract

Key Points Kidney pathology in scleroderma renal crisis was heterogeneous, with three histologic patterns of kidney injury identified by hierarchical cluster analysis. Creatinine, acute arteriolar thrombotic microangiopathy, and onion skinning in small arteries were associated with a higher risk of kidney failure. Complement system was activated in these injured vessels. Background Scleroderma renal crisis (SRC) is a severe complication of systemic sclerosis that is associated with higher morbidity and mortality. However, limited data are currently available regarding the factors affecting kidney outcome during SRC. The objective of this study was to describe kidney histopathology in SRC and to evaluate its association with kidney failure. Methods We performed a French multicenter retrospective study that included 65 patients who underwent a kidney biopsy in the context of SRC between 2006 and 2020. Nonsupervised hierarchical cluster analysis was used to identify histologic patterns. Cox model was performed to estimate the hazard ratios associated with histologic parameters for kidney failure, defined as the need for long-term dialysis therapy or eGFR <15 ml/min per 1.73 m 2 at the last follow-up. Multiplexed sequential immunofluorescence and proximity ligation assay was used in kidney biopsies to analyze complement system activation. Results Kidney pathology in SRC was more heterogeneous than expected, with three histologic patterns of kidney injury identified by cluster analysis. Multivariable analysis showed that together with creatinine at presentation, acute arteriolar thrombotic microangiopathy and onion skinning in small arteries were independently associated with the risk of kidney failure. Multiplex immunofluorescence identified fractions from the complement classical pathway in arterioles and arteries in SRC, while proximity ligation experiments confirmed the in situ activation of classical pathway C3 convertase. Complement terminal pathway fraction C5b-9 was localized in injured arteries. Conclusions This study shows that the clinical definition of SRC encompasses heterogeneity in the patterns of kidney injury. Acute arteriolar thrombotic microangiopathy and onion skinning were associated with kidney failure. Complement system was activated in these injured vessels.

Journal of the American Society of NephrologyVol. 36(11)
Hôpital Necker-Enfants Malades (FR), Inserm (FR), Université de Montpellier (FR), Université Paris Cité (FR), Aix-Marseille Université (FR), Université de Lille (FR), University of Reunion Island (RE), Centre Hospitalier Universitaire de Lille (FR), Sorbonne Université (FR), Institut Necker Enfants Malades (FR), Centre Hospitalier Universitaire de La Réunion (RE), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Lille’s Cardiology Hospital (FR), Sorbonne Paris Cité (FR), Centre de Recherche des Cordeliers (FR), Hôpital Cochin (FR), Hôpital de la Conception (FR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Européen Georges-Pompidou (FR), Hôpital Saint-Antoine (FR), Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine (FR), Centre Hospitalier Sud Francilien (FR), Pitié-Salpêtrière Hospital (FR), Metabolism and Renal Physiology (FR), Université d'été de Boulogne-sur-Mer (FR), Centre Hospitalier de Valenciennes (FR), Hôpital Tenon (FR), Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée, Université de Nîmes (FR)
Good health and well-being
Openalex Percentile: Top 6%
Systemic Sclerosis and Related Diseases
4.41
DOISourceOpenAlex
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