Peritoneal dialysis impairs nitric oxide homeostasis and may predispose infants with low systolic blood pressure to cerebral ischemia

Mattias Carlström, Carmen Cananau, Antonio Checa, Katarina Wide, Lisa Sartz, Anders Svensson, Craig E. Wheelock, Susanne Westphal, Zivile Békássy, Peter Bárány, Jon O. Lundberg, Sverker Hansson, Eddie Weitzberg, Rafael T. Krmar

Research output: Contribution to journalArticlepeer-review

Abstract

Background & purpose Infants on chronic peritoneal dialysis (PD) have an increased risk of developing neurological morbidities; however, the underlying biological mechanisms are poorly understood. In this clinical study, we investigated whether PD-mediated impairment of nitric oxide (NO) bioavailability and signaling, in patients with persistently low systolic blood pressure (SBP), can explain the occurrence of cerebral ischemia. Methods & results Repeated blood pressure measurements, serial neuroimaging studies, and investigations of systemic nitrate and nitrite levels, as well as NO signaling, were performed in ten pediatric patients on PD. We consistently observed the loss of both inorganic nitrate (-17 ± 3%, P < 0.05) and nitrite (-34 ± 4%, P < 0.05) during PD, which may result in impairment of the nitrate-nitrite-NO pathway. Indeed, PD was associated with significant reduction of cyclic guanosine monophosphate levels (-59.4 ± 15%, P < 0.05). This reduction in NO signaling was partly prevented by using a commercially available PD solution supplemented with l-arginine. Although PD compromised nitrate-nitrite-NO signaling in all cases, only infants with persistently low SBP developed ischemic cerebral complications. Conclusions Our data suggests that PD impairs NO homeostasis and predisposes infants with persistently low SBP to cerebral ischemia. These findings improve current understanding of the pathogenesis of infantile cerebral ischemia induced by PD and may lead to the new treatment strategies to reduce neurological morbidities.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalNitric Oxide - Biology and Chemistry
Volume58
DOIs
Publication statusPublished - 2016 Aug 31

Subject classification (UKÄ)

  • Urology and Nephrology
  • Pediatrics
  • Other Clinical Medicine

Free keywords

  • Blood pressure
  • Cerebral ischemia
  • cGMP
  • Chronic kidney disease (CKD)
  • Dialysis
  • Nitrate
  • Nitric oxide
  • Nitric oxide synthase (NOS)
  • Nitrite

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