Dataset Information

Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

ABSTRACT:

Background

Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.

Methods

Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD).

Results

Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.

Conclusions

Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.

SUBMITTER: Moser MA

PROVIDER: S-EPMC4915675 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

Moser Michael A J MA Arcand Steve S Lin Han-Bin HB Wojnarowicz Chris C Sawicka Jolanta J Banerjee Tamalina T Luo Yigang Y Beck Gavin R GR Luke Patrick P PP Sawicki Grzegorz G

PloS one 20160621 6

<h4>Background</h4>Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.<h4>Methods</h4>Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gel ...[more]

PMID: 27327879

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Project description:BackgroundCardiac surgery-associated acute kidney injury (AKI) is an adverse outcome that increases morbidity and mortality in patients undergoing cardiac surgical procedures. To date, the use of serum creatinine levels as an early indicator of AKI has limitations because of its slow rise and poor predictive accuracy for renal injury. This delay in diagnosis may lead to prolonged initiation in treatment and increased risk for adverse outcomes.ObjectiveThis pilot study explores serum and urine matrix metalloproteinases (MMPs)-2 and MMP-9 and their association, and potentially earlier detection of AKI in patients following cardiopulmonary bypass (CPB)-supported cardiac surgery. We hypothesize that increased activity of serum and urine levels MMP-2 and/ or MMP-9 are associated with AKI. Furthermore, MMP-2 and/ or MMP-9 may provide earlier identification of AKI as compared with serum levels of creatinine.MethodsDuring the study period, there were 150 CPB-supported surgeries, 21 of which developed AKI according to the Kidney Disease Improving Global Outcomes criteria. We then selected a sample of 21 matched cases from those patients who went through the surgery without developing AKI. Primary outcomes were the measurement via gel zymography of the serum and urine activity of MMP-2 and MMP-9 drawn at the following intervals: pre-CPB; 10-minute post-CPB; and 4-hour post-CPB time points. Secondary variables were the measurement of serum creatinine, intensive care unit (ICU) fluid balance, and length of ICU stay.ResultsAt the 10-minute and 4-hour post-CPB time points, the serum MMP-2 activity of AKI patients were significantly higher as compared with non-AKI patients (P < .001 and P = .004), respectively. Similarly, at the 10-minute and 4-hour post-CPB time points, the serum MMP-9 activity of AKI patients was significantly higher as compared with non-AKI patients (P = .001 and P = .014), respectively. The activity of urine MMP-2 and MMP-9 of AKI patients was significantly higher as compared with non-AKI patients at all 3 time points (P = .004, P < .001, P < .001), respectively.ConclusionAlthough the pilot study may have limitations, it has demonstrated that the serum and urine levels of activity of MMP-2 and MMP-9 are associated with the clinical endpoint of AKI and appear to have earlier rising levels as compared with those of serum creatinine. Furthermore, in depth, exploration is underway with a larger sample size to attempt validation of the analytical performance and reproducibility of the assay for MMP-2 and MMP-9 to aid in earlier diagnosis of AKI following CPB-supported cardiac surgery.

Dataset Information

Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

Background

Methods

Results

Conclusions

Publications

Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

Similar Datasets

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