title: Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease.
abstract: BACKGROUND
  Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported to improve cellular repair mechanisms.
  
  
  METHODS
  We studied whether exposing CKD rat BMCs ex vivo to pravastatin improved their in vivo therapeutic efficacy in CKD and compared this to systemic in vivo treatment. Six weeks after CKD induction, healthy BMCs, healthy pravastatin-pretreated BMCs, CKD BMCs or CKD pravastatin-pretreated BMCs were injected into the renal artery of CKD rats.
  
  
  RESULTS
  At 6 weeks after BMC injection renal injury was reduced in pravastatin-pretreated CKD BMC recipients vs. CKD BMC recipients. Effective renal plasma flow was lower and filtration fraction was higher in CKD BMC recipients compared to all groups whereas there was no difference between pravastatin-pretreated CKD BMC and healthy BMC recipients. Mean arterial pressure was higher in CKD BMC recipients compared to all other groups. In contrast, 6 weeks of systemic in vivo pravastatin treatment had no effect. In vitro results showed improved migration, decreased apoptosis and lower excretion of pro-inflammatory Chemokine (C-X-C Motif) Ligand 5 in pravastatin-pretreated CKD BMCs.
  
  
  CONCLUSIONS
  Short ex vivo exposure of CKD BMC to pravastatin improves CKD BMC function and their subsequent therapeutic efficacy in a CKD setting, whereas systemic statin treatment did not provide renal protection.
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. a.n.vankoppen-2@umcutrecht.nl.|Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK, Leiden, The Netherlands. a.n.vankoppen-2@umcutrecht.nl.
authors.forename: Arianne
authors.initials: A
authors.lastname: van Koppen
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. d.a.papazova@umcutrecht.nl.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Papazova
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. n.r.oosterhuis@umcutrecht.nl.
authors.forename: Nynke R
authors.initials: NR
authors.lastname: Oosterhuis
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. h.gremmels@umcutrecht.nl.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Gremmels
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. r.giles@umcutrecht.nl.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Giles
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. j.o.fledderus@umcutrecht.nl.
authors.forename: Joost O
authors.initials: JO
authors.lastname: Fledderus
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. j.a.joles@umcutrecht.nl.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
authors.affiliation: Department of Nephrology & Hypertension, University Medical Center Utrecht, F03.223, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. m.c.verhaar@umcutrecht.nl.
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
mesh_terms: D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D001835:Body Weight; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D054365:Chemokine CXCL5 / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005919:Glomerular Filtration Rate; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000502:physiology; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D051436:Renal Insufficiency, Chronic / Q000473:pathology* / Q000628:therapy / Q000662:veterinary; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D054365:Chemokine CXCL5; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin