AKI in kidney transplant recipients—here to stay

Nehus, Edward; Devarajan, Prasad

doi:10.1038/nrneph.2012.40

Cited by 4 publications

(6 citation statements)

References 9 publications

(13 reference statements)

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“…Not only is renal replacement therapy a life-saving procedure, but it also significantly improves the patient's quality of life (9,11,20,47). Ischemiareperfusion injury (IRI) is one of the most serious pitfalls in kidney transplantation and considered as the most critical nonspecific factor for both early and late allograft dysfunction (6,21,48).…”

Section: Introductionmentioning

confidence: 99%

A mouse model of renal ischemia-reperfusion injury solely induced by cold ischemia

Jin

Wang

Zhang

et al. 2019

American Journal of Physiology-Renal Physiology

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Transplanted kidneys usually experience several episodes of ischemia, including cold ischemia during allograft storage in preservation solution. However, previous studies focusing on cold renal ischemia were only carried out in vitro or ex vivo. In the present study, we developed and characterized an in vivo mouse model of renal ischemia-reperfusion injury (IRI) induced exclusively by cold ischemia. C57BL/6 mice underwent right kidney nephrectomy, and the left kidney was kept cool with circulating cold saline in a kidney cup, while body temperature was maintained at 37°C. We clamped the renal pedicle and flushed out the blood inside the kidney with cold saline via an opening on the renal vein. The severity of renal IRI was examined with different ischemic durations. We found that the mice with <2 h of cold ischemia exhibited no significant changes in renal function or histopathology; animals with 3 or 4 h of cold ischemia developed into mild to moderate acute kidney injury with characteristic features, including the elevation in plasma creatinine concentration and reduction in glomerular filtration rate and tubular necrosis, followed by a subsequent recovery. However, mice with 5 h of cold ischemia died in a few days with severe acute kidney injury. In summary, we generated a mouse model of renal IRI induced exclusively by cold ischemia, which mimics graft cold storage in preservation solution, and renal function can be evaluated in vivo.

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Section: Introductionmentioning

confidence: 99%

A mouse model of renal ischemia-reperfusion injury solely induced by cold ischemia

Jin

Wang

Zhang

et al. 2019

American Journal of Physiology-Renal Physiology

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“…Kidney injury due to cold storage-associated transplantation is known to be a major cause of delayed graft function and a potential contributor of chronic allograft nephropathy. 1,3,4 Transplanted kidneys usually undergo several episodes of ischemia, including cold ischemia during organ storage in preservation solutions as well as warm ischemia during organ harvesting and transplantation surgeries. 1,4 Under these conditions, dysfunction and the loss of renal proximal tubular cells play a critical role in the pathogenesis of AKI, responsible for deteriorated renal function and structural damage.…”

mentioning

confidence: 99%

“…1,3,4 Transplanted kidneys usually undergo several episodes of ischemia, including cold ischemia during organ storage in preservation solutions as well as warm ischemia during organ harvesting and transplantation surgeries. 1,4 Under these conditions, dysfunction and the loss of renal proximal tubular cells play a critical role in the pathogenesis of AKI, responsible for deteriorated renal function and structural damage. [4][5][6][7] The mechanism of proximal tubular cell injury and death in AKI is complex, but it includes mitochondrial damage.…”

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confidence: 99%

“…1,4 Under these conditions, dysfunction and the loss of renal proximal tubular cells play a critical role in the pathogenesis of AKI, responsible for deteriorated renal function and structural damage. [4][5][6][7] The mechanism of proximal tubular cell injury and death in AKI is complex, but it includes mitochondrial damage. [8][9][10] In particular, there is an early disruption of mitochondrial dynamics in ischemic AKI, resulting in mitochondrial fragmentation that contributes to proximal tubular cell injury and death.…”

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confidence: 99%

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Protein Kinase C-δ Mediates Kidney Tubular Injury in Cold Storage–Associated Kidney Transplantation

Zhu

Zhang

Song

et al. 2020

JASN

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BackgroundKidney injury associated with cold storage is a determinant of delayed graft function and the long-term outcome of transplanted kidneys, but the underlying mechanism remains elusive. We previously reported a role of protein kinase C-δ (PKCδ) in renal tubular injury during cisplatin nephrotoxicity and albumin-associated kidney injury, but whether PKCδ is involved in ischemic or transplantation-associated kidney injury is unknown.MethodsTo investigate PKCδ’s potential role in injury during cold storage–associated transplantation, we incubated rat kidney proximal tubule cells in University of Wisconsin (UW) solution at 4°C for cold storage, returning them to normal culture medium at 37°C for rewarming. We also stored kidneys from donor mice in cold UW solution for various durations, followed by transplantation into syngeneic recipient mice.ResultsWe observed PKCδ activation in both in vitro and in vivo models of cold-storage rewarming or transplantation. In the mouse model, PKCδ was activated and accumulated in mitochondria, where it mediated phosphorylation of a mitochondrial fission protein, dynamin-related protein 1 (Drp1), at serine 616. Drp1 activation resulted in mitochondrial fission or fragmentation, accompanied by mitochondrial damage and tubular cell death. Deficiency of PKCδ in donor kidney ameliorated Drp1 phosphorylation, mitochondrial damage, tubular cell death, and kidney injury during cold storage–associated transplantation. PKCδ deficiency also improved the repair and function of the renal graft as a life-supporting kidney. An inhibitor of PKCδ, δV1-1, protected kidneys against cold storage–associated transplantation injury.ConclusionsThese results indicate that PKCδ is a key mediator of mitochondrial damage and renal tubular injury in cold storage–associated transplantation and may be an effective therapeutic target for improving renal transplant outcomes.

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“…This study measured the accuracy of the International Classification of Diseases, Tenth Revision ( ICD-10 ) code N17x for AKI in kidney transplant recipients admitted to hospital. We hypothesized that the ICD-10 code would more accurately identify AKI in the kidney transplant population compared to the general population because kidney transplant patients have a higher prevalence of AKI, are more likely to have their kidney function followed closely, and are more likely to have a nephrologist involved in their care during a hospital admission [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

Validation of Administrative Database Codes for Acute Kidney Injury in Kidney Transplant Recipients

Molnar

Walraven

McArthur

et al. 2016

Can J Kidney Health Dis

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BackgroundValidation studies of acute kidney injury (AKI) diagnostic codes performed in the general population have shown poor sensitivity, but the accuracy of such codes in the kidney transplant population remains unknown.ObjectiveThe objective of this study is to determine the accuracy of AKI diagnostic codes in kidney transplant recipients. We hypothesized that the sensitivity of diagnostic codes would be significantly greater in the kidney transplant population since these patients are closely followed by nephrologists and are more likely to have serum creatinine measured.DesignThe design is a population-based retrospective cohort study using healthcare administrative and laboratory databases.SettingThe setting is in Southwestern Ontario and Ottawa, Ontario, Canada, from 2003 to 2012.PatientsWe included first-time kidney transplant recipients admitted to hospital for whom serum creatinine was measured in hospital and within 6 months prior (n = 524).MethodsPatients meeting the Acute Kidney Injury Network (AKIN) classification serum creatinine change criteria were classified as having AKI. We determined the sensitivity, specificity, and negative and positive predictive values for the ICD-10-CA code for AKI when present as an admission diagnosis, most responsible diagnosis, or any diagnosis compared to a reference standard of AKI defined by the AKIN criteria (stage 1 or greater, stage 2 or greater, or stage 3).ResultsForty-five percent of included kidney transplant patients had a diagnosis of AKI. The most sensitive coding algorithm (reference standard AKIN stage 2 or greater, ICD-10 code present as any diagnosis) had a sensitivity of 42.1 % (95 % CI 31.7, 53.3), a specificity of 90.6 % (95 % CI 87.6, 93.0), and a positive likelihood ratio of 4.5. The median (IQR) rise in serum creatinine from baseline in patients with and without AKI codes was 104 (57 to 158) μmol/L and 16 (−3 to 41) μmol/L, respectively (Mann-Whitney test, p < 0.0001).LimitationsThe low sensitivity of the AKI code may be due to an alternative diagnosis of acute rejection being assigned in certain cases. The cause of AKI could not be determined.ConclusionsSimilar to the general population, the ICD-10 N17x code misses many kidney transplant patients with AKI during their hospitalization. This makes the code unusable for studying the incidence and consequences of AKI in hospitalized kidney transplant patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40697-016-0108-7) contains supplementary material, which is available to authorized users.

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AKI in kidney transplant recipients—here to stay

Cited by 4 publications

References 9 publications

A mouse model of renal ischemia-reperfusion injury solely induced by cold ischemia

A mouse model of renal ischemia-reperfusion injury solely induced by cold ischemia

Protein Kinase C-δ Mediates Kidney Tubular Injury in Cold Storage–Associated Kidney Transplantation

Validation of Administrative Database Codes for Acute Kidney Injury in Kidney Transplant Recipients

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