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Capillary rarefaction is more closely associated with CKD progression after cisplatin, rhabdomyolysis, and ischemia-reperfusion-induced AKI than renal fibrosis.
Menshikh, Anna; Scarfe, Lauren; Delgado, Rachel; Finney, Charlene; Zhu, Yuantee; Yang, Haichun; de Caestecker, Mark P.
Afiliação
  • Menshikh A; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Scarfe L; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Delgado R; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Finney C; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Zhu Y; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Yang H; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
  • de Caestecker MP; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Am J Physiol Renal Physiol ; 317(5): F1383-F1397, 2019 11 01.
Article em En | MEDLINE | ID: mdl-31509009
ABSTRACT
Acute kidney injury (AKI) is a strong independent predictor of mortality and often results in incomplete recovery of renal function, leading to progressive chronic kidney disease (CKD). Many clinical trials have been conducted on the basis of promising preclinical data, but no therapeutic interventions have been shown to improve long-term outcomes after AKI. This is partly due to the failure of preclinical studies to accurately model clinically relevant injury and long-term outcomes on CKD progression. Here, we evaluated the long-term effects of AKI on CKD progression in three animal models reflecting diverse etiologies of AKI repeat-dose cisplatin, rhabdomyolysis, and ischemia-reperfusion injury. Using transdermal measurement of glomerular filtration rate as a clinically relevant measure of kidney function and quantification of peritubular capillary density to measure capillary rarefaction, we showed that repeat-dose cisplatin caused capillary rarefaction and decreased renal function in mice without a significant increase in interstitial fibrosis, whereas rhabdomyolysis-induced AKI led to severe interstitial fibrosis, but renal function and peritubular capillary density were preserved. Furthermore, long-term experiments in mice with unilateral ischemia-reperfusion injury showed that restoration of renal function 12 wk after a contralateral nephrectomy was associated with increasing fibrosis, but a reversal of capillary rarefaction was seen at 4 wk. These data demonstrate that clear dissociation between kidney function and fibrosis in these models of AKI to CKD progression and suggest that peritubular capillary rarefaction is more strongly associated with CKD progression than renal fibrosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rabdomiólise / Traumatismo por Reperfusão / Cisplatino / Insuficiência Renal Crônica / Injúria Renal Aguda / Rarefação Microvascular Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rabdomiólise / Traumatismo por Reperfusão / Cisplatino / Insuficiência Renal Crônica / Injúria Renal Aguda / Rarefação Microvascular Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article