Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Yannick Binois^{1

2}, David Buob³, Marie-Sophie Meuleman^{4

5}, Idris Boudhabhay^{2

4

5}, Pierre Isnard⁶, Marion Rabant⁶, Viviane Gnemmi⁷, Laurent Daniel⁸, Isabelle Brocheriou⁹, Clement Gosset¹⁰, Marie Frimat¹¹, Thomas Quémeneur¹², Rafik Mesbah¹³, Noemie Jourde-Chiche¹⁴, Olivier Moranne¹⁵, Pierre Housset¹⁶, Emmanuel Esteve¹⁷, Alexis Mathian¹⁸, Sebastien Rivière¹⁹, Aurélie Hummel²⁰, Luc Mouthon^{2

21}, Benjamin Chaigne^{2

21}, Anne-Lyse Langlois¹, Eric Thervet^{1

2}, Olivier Aubert^{2

20}, Lubka Roumenina^{4

5}, Sophie Chauvet^{1

2

4

5}, Alexandre Karras^{1

2}, Jean-Paul Duong-Van-Huyen^{2

4

5

6}

Affiliations

¹ AP-HP, Nephrology Department, European Georges Pompidou Hospital, Paris, France.
² Paris Cité University, Health Science, Paris, France.
³ AP-HP, Pathology Department, Tenon Hospital, Paris, France.
⁴ INSERM UMRS1138 team "Inflammation, Complement and Cancer," Cordeliers Research Center, Paris, France.
⁵ University Hospital Federation (FHU) COMET, Paris, France.
⁶ AP-HP, Pathology Department, Necker- Enfants Malades Hospital, Paris, France.
⁷ Pathology Department, Lille University Hospital Center, Lille, France.
⁸ C2VN, INSERM, INRAE et AP-HM, Centre de Néphrologie et Transplantation Rénale, CHU de la Conception, Aix-Marseille University, Marseille, France.
⁹ AP-HP, Pathology Department, La Pitié Salpêtrière Hospital, Paris, France.
¹⁰ Nephrology Department, La Réunion University Hospital Center, Saint-Denis, France.
¹¹ CHU Lille, Nephrology Department, Inserm U1167 - RID-AGE, University of Lille, Lille, France.
¹² Nephrology Department, Valenciennes Hospital Center, Valenciennes, France.
¹³ Nephrology Department, Boulogne Sur Mer Hospital Center, Boulogne Sur Mer, France.
¹⁴ AP-HM, Nephrology Department, La Conception Hospital, Marseille, France.
¹⁵ Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France.
¹⁶ Nephrology Department, Centre Hospitalier Sud Francilien Hospital, Corbeil-Essonnes, France.
¹⁷ APHP, Nephrology Department, Nephrology and Dialysis, Sorbonne University, INSERM U1155 Corakid, Hopital Tenon, Paris, France.
¹⁸ AP-HP, Internal Medicine Department, La Pitié Salpêtrière Hospital, Paris, France.
¹⁹ Service de Médecine Interne, AP-HP, Hôpital Saint Antoine, Sorbonne Université, Paris, France.
²⁰ AP-HP, Nephrology Department, Necker - Enfants malades Hospital, Paris, France.
²¹ AP-HP, Internal Medicine Department, Cochin Hospital, Paris, France.

PMID: 40333024
PMCID: PMC12591686 (available on 2026-11-01)
DOI: 10.1681/ASN.0000000720

Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Yannick Binois et al. J Am Soc Nephrol. 2025.

. 2025 Nov 1;36(11):2201-2212.

doi: 10.1681/ASN.0000000720. Epub 2025 May 7.

Authors

Affiliations

¹ AP-HP, Nephrology Department, European Georges Pompidou Hospital, Paris, France.
² Paris Cité University, Health Science, Paris, France.
³ AP-HP, Pathology Department, Tenon Hospital, Paris, France.
⁴ INSERM UMRS1138 team "Inflammation, Complement and Cancer," Cordeliers Research Center, Paris, France.
⁵ University Hospital Federation (FHU) COMET, Paris, France.
⁶ AP-HP, Pathology Department, Necker- Enfants Malades Hospital, Paris, France.
⁷ Pathology Department, Lille University Hospital Center, Lille, France.
⁸ C2VN, INSERM, INRAE et AP-HM, Centre de Néphrologie et Transplantation Rénale, CHU de la Conception, Aix-Marseille University, Marseille, France.
⁹ AP-HP, Pathology Department, La Pitié Salpêtrière Hospital, Paris, France.
¹⁰ Nephrology Department, La Réunion University Hospital Center, Saint-Denis, France.
¹¹ CHU Lille, Nephrology Department, Inserm U1167 - RID-AGE, University of Lille, Lille, France.
¹² Nephrology Department, Valenciennes Hospital Center, Valenciennes, France.
¹³ Nephrology Department, Boulogne Sur Mer Hospital Center, Boulogne Sur Mer, France.
¹⁴ AP-HM, Nephrology Department, La Conception Hospital, Marseille, France.
¹⁵ Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, Nîmes, France.
¹⁶ Nephrology Department, Centre Hospitalier Sud Francilien Hospital, Corbeil-Essonnes, France.
¹⁷ APHP, Nephrology Department, Nephrology and Dialysis, Sorbonne University, INSERM U1155 Corakid, Hopital Tenon, Paris, France.
¹⁸ AP-HP, Internal Medicine Department, La Pitié Salpêtrière Hospital, Paris, France.
¹⁹ Service de Médecine Interne, AP-HP, Hôpital Saint Antoine, Sorbonne Université, Paris, France.
²⁰ AP-HP, Nephrology Department, Necker - Enfants malades Hospital, Paris, France.
²¹ AP-HP, Internal Medicine Department, Cochin Hospital, Paris, France.

PMID: 40333024
PMCID: PMC12591686 (available on 2026-11-01)
DOI: 10.1681/ASN.0000000720

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 m² 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.

Keywords: AKI; acute kidney failure; nephrology; renal pathology.

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Conflict of interest statement

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/F227.

References

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Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Affiliations

Histologic Features Associated with Kidney Survival in Scleroderma Renal Crisis

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials

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