Kidney Week

Abstract: SA-PO441

A Multicohort Biomarker Study in Patients with Advanced CKD on Peritoneal Dialysis or Hemodialysis and in Healthy Volunteers Investigating Inflammatory Markers

Session Information

• Home Dialysis - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

• Junge, Guido, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Guido Junge, MD, PhD

• Aregger, Fabienne, Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

Fabienne Aregger, MD

• Uehlinger, Dominik E., Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

Dominik E. Uehlinger, MD

• Kuhlmann, Martin K., Department of Nephrology, Vivantes Clinic in Friedrichshain, Berlin, Germany

Martin K. Kuhlmann, MD

• Seibert, Eric, Nephrology Center, Villingen-Schwenningen, Germany

Eric Seibert, MD, FASN

• Do Valle Duraes, Fernanda, Novartis Pharma AG, Basel, Switzerland

Fernanda Do Valle Duraes, PhD

• Höppli, Romy, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Romy Höppli, PhD

• Orjuela Leon, Anette Carolina, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Anette Carolina Orjuela Leon, PharmD, PhD

• Malinverni, Claire, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Claire Malinverni, MSc

• Jeanneau, Karine, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Karine Jeanneau, MSc

• Wieczorek, Grazyna, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Grazyna Wieczorek, DVM

• Seroutou, Abdelkader, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Abdelkader Seroutou

• Hohenstein, Bernd, Nephrology Center, Villingen-Schwenningen, Germany

Bernd Hohenstein, MD, FASN

Background

CKD and ESKD lead to a significant increase in inflammatory cytokines contributing to long-term complications such as anemia, malnutrition, atherosclerosis, and CV disease. This trial explores the potential role of the NLRP3 inflammasome and complement system for the underlying chronic inflammation in CKD patients w/wo KRT.

Methods

BASICHR0052 is a multi-center, prospective biomarker study conducted in pre-KRT CKD4/5, and ESKD patients on KRT (PD or HD at RRT start, month(M) 2-6, or >M12) to assess inflammatory markers in plasma and PD dialysate. Healthy volunteers' (HVs) samples from 12 subjects were collected as part of another study.

Results

46 subjects (17 CKD4/5, 16 HD, 13PD) were enrolled. We observed a stepwise increase of apoptosis-associated speck-like protein containing CARD (ASC), a marker of NLRP3 activation, IL-18, IL-18BPa and CXCL9 plasma concentrations from HV to CKD and ESKD patients. Key inflammatory cytokines such as IL-1RA, IL-18 and IL-6 were higher in all CKD groups compared to HV. ASC and CXCL9 were removed during HD. IL-6 was higher in the PD dialysate compared to plasma levels, suggesting a modality related, inflammatory peritoneal component.
Alternative complement pathway activation was evidenced by significant increase of iC3b and Bb in CKD and HD compared with HV. Dialysis raised levels of both fragments. Significant increase of FD in CKD and HD pre-dialysis were also observed. No significant difference was observed in TCC, FB and C3.

Conclusion

Overall, subjects with advanced CKD stages and especially those under KRT presented evidence of chronic activation of the NLRP3 inflammasome and the complement system. HD resulted in reduction of ASC and CXCL9 and an increase of iC3b and Bb. IL 6 concentrations were comparable between HD and PD patients but were higher in dialysate of PD patients compared to plasma. Further studies are required to validate those findings as potential new therapeutic targets for patients with advanced CKD w/wo RRT.

Funding

• Commercial Support – Novartis Pharma AG