Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging

Sci Adv. 2019 Aug 14;5(8):eaaw8357. doi: 10.1126/sciadv.aaw8357. eCollection 2019 Aug.

Abstract

Chronic Kidney Disease (CKD) is a cardinal feature of methylmalonic acidemia (MMA), a prototypic organic acidemia. Impaired growth, low activity, and protein restriction affect muscle mass and lower serum creatinine, which can delay diagnosis and management of renal disease. We have designed an alternative strategy for monitoring renal function based on administration of a pH sensitive MRI agent and assessed this in a mouse model. This protocol produced three metrics: kidney contrast, ~4% for severe renal disease mice compared to ~13% and ~25% for moderate renal disease and healthy controls, filtration fraction (FF), ~15% for severe renal disease mice compared to ~79% and 100% for moderate renal disease and healthy controls, and variation in pH, ~0.45 units for severe disease mice compared to 0.06 and 0.01 for moderate disease and healthy controls. Our results demonstrate that MRI can be used for early detection and monitoring of CKD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Animals
  • Disease Models, Animal
  • Glomerular Filtration Rate / physiology
  • Kidney / diagnostic imaging*
  • Kidney / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Perfusion Imaging / methods
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / diagnostic imaging*
  • Renal Insufficiency, Chronic / pathology*

Supplementary concepts

  • Methylmalonic acidemia