In situ lactate dehydrogenase activity: a novel renal cortical imaging biomarker of tubular injury?

Abstract

Renal ischemia-reperfusion injury is the state of which a tissue experiences injury after a phase of restrictive blood supply and recirculation. Ischemia-reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis, and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen, or renal histology. However, currently, there are no precise methods to directly assess renal injury state noninvasively. Hyperpolarized C-pyruvate MRI enables noninvasive accurate quantification of the in vivo conversion of pyruvate to lactate, alanine, and bicarbonate. In the present study, we investigated the in situ alterations of metabolic conversion of pyruvate to lactate, alanine, and bicarbonate in a unilateral I/R-I rat model with 30 min and 60 min of ischemia followed by 24 h of reperfusion. The pyruvate conversion was unaltered compared with sham in the 30 min I/R-I group, while a significant reduced metabolic conversion was found in the postischemic kidney after 60 min of ischemia. This indicates that after 30 min of ischemia, the kidney maintains normal metabolic function in spite of decreased kidney function, whereas the postischemic kidney after 60 min of ischemia show a generally reduced metabolic enzyme activity concomitant with a reduced kidney function. We have confidence that these findings can have a high prognostic value in prediction of kidney injury and the outcome of renal injury.

Hyperpolarized 13C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model

“…Our finding of decreased HP 13 C Bic production following IRI is in agreement with a recent study by Nielsen et al, which reported lower HP 13 C Pyr conversion to Bic in a rat model of unilateral IRI with 60 min of ischemia followed by 24 h of reperfusion. However, the investigators in that study also showed a decrease in 13 C Pyr conversion to Lac in the kidneys subjected to IRI.…”

“…The discrepancy between the findings is probably attributable to the time of assessment. The study by Nielsen et al was performed at 24 h following IRI when many renal tubules were probably necrotic, with attendant loss of cellular LDH and low Pyr conversion to Lac . Indeed, other murine studies have shown significantly depressed renal LDH levels 18–24 h following IRI as a result of LDH release from necrotic cells .…”

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

“…This signal enhancement allows real-time imaging of metabolic pathways using 13 C-labeled endogenous substrates15. We have recently demonstrated metabolic alterations in post-ischemic unilateral IRI rats following hyperpolarized [1- 13 C]pyruvate infusion16. Showing an upregulation of the anaerobic pathways, similarly to what has been demonstrated in diabetic kidney171819, albeit lower total turnover, most likely caused by necrosis.…”

Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

“…The rest of the arterial blood was spun for plasma purification in heparin‐coated tubes. Kidney tissue and urine were collected as previously described …”