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Lactate dehydrogenase activity, a novel renal cortical imaging bio‐marker of tubular injury
Author(s) -
Nielsen Per Mose,
Laustsen Christoffer,
Qi Haiyun,
Nørlinger Thomas,
Mikkelsen Emmeli,
Norregaard Rikke,
StødkildeJørgensen Hans
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1217.10
Subject(s) - acute kidney injury , renal function , medicine , kidney , creatinine , lactate dehydrogenase , ischemia , oxidative stress , magnetic resonance imaging , pathology , chemistry , endocrinology , biochemistry , radiology , enzyme
Renal ischemia/reperfusion injury (I/R‐I) is the leading cause of acute kidney injury (AKI) in several disease states, including hypovolemic shock, sepsis, surgery. Imbalance in energy metabolism and mitochondrial function is a hallmark in I/R‐I which can be caused by mechanisms like oxidative stress, apoptosis and inflammation. Lactate dehydrogenase (LDH) activity has previously been suggested as a renal tubular injury marker, but has a major limitation in the sense that it can only be measured in terminal kidneys. Recent advances in magnetic resonance technology, has allowed hyperpolarized [1‐ 13 C]pyruvate magnetic resonance imaging (MRI) to monitor metabolic changes in real time in situ without ionizing radiation. Thus this procedure allows for investigation of renal tissue injury in concern with I/R‐I, by probing the renal metabolism after I/R‐I and especially the LDH activity. Sixteen Wistar Rats were included in the study. Rats were subjected to unilateral (or bilateral) renal ischemia for 60 min followed by reperfusion for 24 hours (n=8). Sham operated rats were prepared in parallel (n=8). A tail vein catheter was inserted for injection of hyperpolarized [1‐ 13 C]pyruvate before the MRI scanning. Temperature, arterial oxygen saturation and respiration rate were monitored throughout the experiment. After MRI scanning, kidneys were excised and stored for further biochemical analyses. I/R‐I resulted in statistically significantly increased plasma creatinine, BUN and decreased creatinine clearance, indicating AKI. Additionally kidney injury molecule 1 (KIM‐1) was significantly increased in rats subjected to I/R‐I, indicating cellular injury. Hyperpolarized [1‐ 13 C]pyruvate showed a reduced LDH activity in the post‐ischemic kidneys, calculated from pyruvate‐to lactate conversion. This was verified by activity measurements of LDH in terminal kidneys. Using a bilateral I/R‐I model increased LDH activity was also observed in urine samples. Like LDH activity a reduced ALT and PDH activity was also found in the I/R‐I model, calculated from pyruvate‐bicarbonate conversion, and pyruvate‐to‐alanine conversion. An increased LDH mRNA transcription, together with a reduced NADH/NAD + ratio indicates a preference for anaerobic glycolysis in the I/R‐I kidney. This is supported by MR results when comparing lactate‐to‐bicarbonate formation, which individually describes the anaerobic and aerobic glycolysis. In conclusion, a decreased LDH activity is observed in the I/R‐I kidney, and this is correlated with tissue injury. Although the general LDH activity in the I/R‐I kidney is lowered, a weighted preference towards anaerobic metabolism was evident in the I/R‐I kidney. Support or Funding Information Karen Elise Jenens Foundation