Risks and consequences of travel burden on prophylactic granulocyte colony-stimulating factor administration and incidence of febrile neutropenia in an aged Medicare population

Objective: Granulocyte colony-stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. This study examines the impact patient travel burden has on administration of prophylactic G-CSFs and the subsequent impact on FN incidence.

Methods: Medicare claims data were used to identify a cohort of beneficiaries age 65+ with non-myeloid cancers at high risk for FN between January 2012 and December 2014. Driving distance and time were calculated from patient residence ZIP code to the location of G-CSF and/or chemotherapy administration. Regression models were used to estimate the odds of G-CSF prophylaxis relative to patient driving distance and time, and odds of FN incidence relative to timing of G-CSF administration (optimal [days 2–4 after chemotherapy], sub-optimal [same day], or none).

Results: The 52,389 study patients had a mean age of 73.5 years, and were 82% female and 89% white race; 49% had female breast cancer, 12% lung cancer, 15% ovarian cancer, and 24% non-Hodgkin’s lymphoma. Of these high FN risk patients, 69% had at least one prophylactic G-CSF administration within at least one chemotherapy cycle. The percentage of patients receiving prophylactic G-CSFs in the first cycle was 56%. Median travel time was slightly longer for patients who did not receive G-CSFs and patients receiving short-acting vs long-acting G-CSFs. The odds of receiving no G-CSFs were 26–52% higher (depending on cancer type) for patients with a?>80-min one-way travel time, compared to patients traveling <20-min. Concurrently, the odds of FN (using a “narrow” definition) were 18–93% higher for patients who did not receive G-CSFs in the first cycle of chemotherapy.

Conclusions: Travel burden, linked to clinic visits for G-CSF administration following myelosuppressive chemotherapy, is associated with sub-optimal use of G-CSF prophylaxis, which may result in a higher incidence of FN.     

An evaluation of peripapillar choroidal thickness in patients receiving systemic isotretinoin treatment

Purpose: Oral isotretinoin (13-cis retinoic acid, 13-cis RA) was approved for severe acne treatment by the FDA in 1982. The ocular side effects associated with oral isotretinoin use are mostly dose-dependent. Numerous ocular pathologies affect peripapillary choroidal layer primarily or indirectly.

Objective: Evaluation of the peripapillary choroidal layer in the patients receiving oral isotretinoin therapy may aid in explaining the pathophysiology of ocular side effects.

Methods: In this study, peripapillary choroidal thickness was assessed in the patients receiving oral isotretinoin treatment via optical coherent tomography technique.

Results: Significant difference was found in the superotemporal and temporal areas.

Conclusion: Oral isotretinoin treatment may affect the thickness of the peripapillary choroidal layer.     

Secondary cannabis use among London drug treatment service clients

Background: Cannabis is the second most commonly used substance after alcohol among people seeking treatment for other drug use, but no statistics are available regarding secondary cannabis use among drug treatment clients.

Objectives: To investigate levels of secondary cannabis use among drug treatment clients and perceived need for support addressing this use among clients and staff.

Methods: Cross-sectional surveys of clients (N?=?295) and staff (N?=?33) were conducted in 2015 at four London drug and alcohol treatment services. Client measures included recent drug use, type of cannabis used, Severity of Dependence Scale for cannabis, and views on secondary cannabis use treatment. Staff measures included definition of problem cannabis use, importance and timing for addressing secondary cannabis use.

Results: Among clients, 39.7% reported recent secondary cannabis use, with 30.8% of these clients meeting criteria for problem use. Problem users were more likely to be interested in receiving treatment for cannabis use than non-problem users (51.4% versus 10.8%, p?<?.001). Nearly half of staff (48.5%) thought secondary cannabis use should be addressed early in treatment.

Conclusions: Two out of five drug treatment clients used cannabis and a third experienced cannabis-related problems. Many are willing to address cannabis use, but defined treatment pathways are needed.     

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis: a retrospective evaluation using Medicare claims

Background: Two recent evaluations reported that many cancer chemotherapy patients discontinue pegfilgrastim prophylaxis (PP) following the first cycle, and that these patients have a higher subsequent risk of febrile neutropenia (FN). Such evidence is based principally on the experience of younger adults with private healthcare coverage, and the generalizability of results to elderly Medicare patients is unknown.

Methods: A matched-cohort design and data from the Medicare Claims Research Identifiable Files were employed. The source population comprised cancer patients aged ≥65 years who received chemotherapy with intermediate/high-risk for FN and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this sub-set, patients who did not receive PP in the cycle of interest (“comparison patients”) were matched to those who received PP in that cycle (“PP patients”); the same process was repeated for subsequent cycles. Odds ratios (OR) for FN (broad and narrow definitions) were estimated using generalized estimating equations.

Results: Among 77,616 elderly patients in the source population, 5.3% did not receive second-cycle PP and were matched to those who did. In cycle 2, FN odds were significantly higher among comparison patients vs PP patients when employing the broad definition (OR?=?1.9, p?<?.001) and the narrow definition (OR?=?2.1, p?<?.001). Results for subsequent cycles (broad definition: OR?=?2.0, p?<?.001; narrow definition: OR?=?2.1, p?<?.001) and for the last cycle (broad definition: OR?=?1.4, p?=?.060; narrow definition: OR?=?1.7, p?=?.055) were largely comparable.

Conclusions: In this large-scale evaluation of elderly Medicare patients who received myelosuppressive chemotherapy and first-cycle PP in recent US clinical practice, FN risk was substantially lower among patients who continued to receive PP in subsequent cycles vs those who discontinued PP.     

Optimisation of the microencapsulation of lavender oil by spray drying

Background: Lavender oil consists of around 100 components and is susceptible to volatilisation and degradation reactions.

Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.

Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.

Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).

Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend.     

Gender,subclinical organ damage and cardiovascular risk stratification in hypertensive patients

Background: The aims of the study were to assess subclinical organ damage in men and women with hypertension and its subsequent effect on cardiovascular risk, and use of new statistical methods for more precise estimation of cardiovascular risk using vascular cardiovascular risk factors: ankle–brachial index (ABI), intima–media thickness (IMT) and pulse wave velocity (PWV).

Methods: We studied 200 patients: 100 hypertensive and 100 normotensive. The parameters we evaluated included: patient age, ABI, IMT, PWV, serum uric acid and serum C-reactive protein (CRP). In addition, the cardiovascular risk according to the SCORE and Framingham scales was assessed.

Results: In the hypertensive group, there were significant correlations between ABI and the Framingham scale in both sexes. In hypertensive women, there were also significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.

In normotensive women, there were significant correlations between ABI and the SCORE scale risk, and between ABI and the Framingham scale risk. In normotensive men, there were significant correlations between PWV and the SCORE scale risk, and between PWV and the Framingham scale risk. Lastly, in the group of normotensive men, there were significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.

The possibility of correctly classifying a patient into the high-risk category by a logistic regression model using synchronous ABI, IMT and PWV was high – 74% for the risk according to the SCORE scale (66% in men, 88% in women), and 98% for the Framingham scale.

Conclusions: The addition of recognized subclinical target organ damage tests to the estimation of cardiovascular risk can significantly strengthen the prevention of cardiovascular disease.

Cardiovascular risk estimation follow-up with ABI, PWV and IMT increased the probability of correctly classifying people, especially women, into an at least high-risk category according to the SCORE scale, which has valuable therapeutic implications.     

Everolimus for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC)

Introduction: PDAC is a lethal malignancy with a clear unmet need; almost all patients fail 1^st, 2^nd, and 3^rd line multi-agent cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) has been identified as a key signaling node enhancing tumor survival and drug resistance in PDAC; hence, it is considered a promising therapeutic target.

Areas covered: We comprehensively reviewed the evidence from preclinical and phase I and II clinical trials, based on the authors’clinical experience and a PubMed, Cochrane library, Embase, and Google Scholar search everolimus + pancreatic cancer.

Expert opinion: Everolimus has not demonstrated efficacy in PDAC; however, an mTOR inhibitor in combination with stroma-targeted therapies may be a promising area to explore in clinical trials.     

Collaboration between patient and pharmacovigilance organizations to gain insight into adults’ experiences with drug use and ADRs for the treatment of ADHD

Background: Patient organizations have good access to patients, which can be of interest in gaining knowledge about patients’ experiences with drugs. The aim of this study is to investigate if a collaboration between a pharmacovigilance center and an ADHD patient organization can give more insight in patients’ experiences with drug use and ADRs for the treatment of AD(H)D.

Methods: Pharmacovigilance Centre Lareb and ADHD patient organization Impuls & Woortblind created a web-based questionnaire asking about patients’ experiences with drug use and ADRs. Patients were approached to participate by e-mail and an open web-link. They were also asked to report ADRs through the official reporting form of Lareb.

Results: A total of 1160 patients completed the questionnaire, of which 75.2% of the respondents experienced ADRs and 60.7% discontinued treatment because of an ADR. More than 70% experienced positive effects of their drugs. Additionally, 5.0% of the respondents reported their ADRs to Lareb.

Conclusions: Collaboration with patient organizations provide useful insight into patients’ experiences with drug use and ADRs taking into account establishing clear ‘rules of engagement’. An active approach to collaborate with patient organizations is a way forward to gain more information about drug use and ADRs in a selective cohort.     

Study description and baseline characteristics of the population enrolled in a multinational,observational study of teriparatide in postmenopausal women with osteoporosis: the Asia and Latin America Fracture Observational Study (ALAFOS)

Objective: To describe the study design and baseline patient characteristics of the Asia and Latin America Fracture Observational Study (ALAFOS) to better understand the profile of patients receiving teriparatide during the course of routine clinical practice in Asia, Latin America, the Middle East and Russia.

Methods: Prospective, observational, non-interventional study in postmenopausal women with osteoporosis who are prescribed teriparatide for up to 24?months, according to local medical standards, with a 12?month post-treatment follow-up.

Measures: Demographics, risk factors for osteoporosis and fractures, history of fracture, prior osteoporosis medications, comorbidities, physical function, back pain and quality of life (QoL).

Results: In total 3031 postmenopausal women (mean age 72.5?years) recruited at 152 sites in 20 countries were analyzed; 62.9% had a history of fragility fracture after age 40 (33.0% of patients with spinal, 14.2% with hip fractures). The mean (SD) bone mineral density T-scores at baseline were ?3.06 (1.40) and ?2.60 (1.05) at the lumbar spine and femoral neck, respectively. At entry, 43.7% of patients were naïve to prior osteoporosis treatments; 40.5% of patients reported ≥1 fall in the past year. The median (Q1; Q3) EuroQoL Visual Analog Scale (EQ-VAS) for perceived overall health status was 60 (50; 80). The mean (SD) worst back pain Numeric Rating Scale in the last 24?hours was 4.6 (3.3).

Conclusions: Our data indicates that patients who were prescribed teriparatide in the ALAFOS participant countries had severe osteoporosis, high prevalence of fractures, disabling back pain and poor QoL. The frequency of patients receiving prior osteoporosis medications was lower than in previous observational studies conducted in other locations.     

Safety profile of non-vitamin K oral anticoagulants (NOACs) from a patient perspective: a web-based cohort event monitoring study

Objectives: Non-vitamin K oral anticoagulants (NOACs) are a relatively new group of anticoagulants. Characteristics of adverse drug reactions (ADRs) as experienced by patients in everyday use have not yet been fully clarified. The aim was to gain insight into the safety profile of NOACs from a patient’s perspective.

Methods: This was a prospective, observational web-based cohort event monitoring study among first-time users of NOACs. Patients were recruited between July 2012 and April 2017. They were invited to complete four web-based questionnaires 2 weeks, 5 weeks, 3 months and 6 months after starting treatment. Information was collected about patient characteristics, drug use, and characteristics of ADRs.

Results: 1748 NOAC users were included. 661 (38%) experienced at least one ADR. The reported ADRs were comparable with the information described in the Summary of Product Characteristics and generally occurred within 1 week after the start. In 59% of ADRs the patients recovered. These ADRs had no impact on the use and dosage of the NOAC in 68%. In total, 9% of the patients discontinued the NOAC because of ADRs.

Conclusion: Overall NOACs were well tolerated by the participants. Most reported ADRs occurred within 1 week after the start. Patients recovered from most ADRs without changes to the use of the NOAC.     

Stress-related upper gastrointestinal bleeding in adult neurocritical care patients: a Chinese multicenter,retrospective study

Objective: China has limited data on stress-related gastrointestinal ulcers in patients admitted for neurosurgical care. This study evaluated the incidence of upper gastrointestinal bleeding (UGIB) and use of stress ulcer prophylaxis (SUP) in Chinese neurocritical care patients (Glasgow Coma Scale [GCS] score ≤10).

Methods: This multicenter, retrospective study was performed from January 2015 to July 2015. Medical records of 1468 patients hospitalized during 2014 were reviewed. An estimated UGIB incidence rate of 4.4% was considered for precision of 1.3% for estimation of UGIB. The primary endpoint was evaluation of overall incidence of any overt UGIB in ≤14 days after cerebral lesion. Secondary endpoints included incidence of UGIB with or and without clinically significant complications, time to UGIB, associated risk factors and SUP used.

Results: We analyzed 1416 patients (mean age: 53.7?±?14.00 years; males: 62.4%) with cerebral lesions. Overall incidence rate of UGIB ≤14 days was 12.9% (95% CI: 11.2%–14.7%), 0.76% with and 12.1% without significant clinical complications. Average time and duration of bleeding were 2.9?±?3.37 days and 4.2?±?8.4 days, respectively. The most significant risk factors for UGIB were mechanical ventilation for >48?hours (p?<?.0001), UGIB history (p?=?.0026) and use of anticoagulants (p?<?.0001). Acid-suppression drugs were administered for SUP in 79.0% of the patients, whereas 40.5% received hemostatic drugs.

Conclusions: The rate of UGIB incidence was higher than the estimated rate in neurocritical care patients in China, suggesting the need for better management and treatment for stress-related mucosal disease in China. History of UGIB, mechanical ventilation and/or anticoagulants significantly affected UGIB.

ClinicalTrials registry number: NCT02316990.     

Predictors of systemic therapy sequences following a CDK 4/6 inhibitor-based regimen in post-menopausal women with hormone receptor positive,HEGFR-2 negative metastatic breast cancer

Objective: To identify systemic treatment in the real-world following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDKi) among post-menopausal women with hormone receptor positive, human epidermal growth factor receptor 2 Negative (HR+/HER2–) metastatic breast cancer (mBC).

Methods: Post-menopausal women with HR+/HER2– mBC were identified from MarketScan claims databases between January 1, 2012 and October 31, 2017. Eligible mBC patients who received a CDKi-based line of therapy following metastasis diagnosis were selected. A line of therapy ended at the earlier of systemic therapy discontinuation, switch to new treatment, or censoring.

Results: In total, 525 patients that received systemic therapy after a CDKi-based line were included (39.6% transitioned from use of a CDKi-based regimen in first line following metastasis diagnosis to any second line, and 60.4% shifted from a CDKi-based [second, third, or fourth line] to a subsequent line). Of post-CDKi second line regimens (n?=?208), 38.0% were endocrine only, 35.6% were chemotherapy-based, 14.4% were everolimus-based, 9.6% were also CDKi-based line, and 2.4% were others. After adjusting for demographic and clinical characteristics, patients transitioning from a CDKi-based line to chemotherapy (vs others) had a trend of being more likely to have recurrent rapidly progressing disease, and were significantly less likely to have the prior CDKi-based line in combination with an AI (both p?<?.05).

Conclusions: This population-based study suggests that rapidly progressing disease, metastatic site location, age, and endocrine therapy partner may be predictive of subsequent systemic therapy regimen selection after progression on a CDKi-based line therapy in patients with HR+/HER2– mBC.     

Cost-effectiveness of pembrolizumab in combination with chemotherapy versus chemotherapy and pembrolizumab monotherapy in the first-line treatment of squamous non-small-cell lung cancer in the US

Objective: To describe the cost-effectiveness of pembrolizumab plus chemotherapy (carboplatin and paclitaxel or nab-paclitaxel; P?+?C) in metastatic, squamous, non-small-cell lung cancer (NSCLC) patients in the US.

Methods: A model comparing P?+?C versus C alone is developed utilizing partitioned survival analysis. Primary clinical efficacy, treatment utilization, health utility and safety data are derived from the KEYNOTE-407 trial and projected over 20?years. Costs for drugs and non-drug disease management are also incorporated. Additionally, the cost-effectiveness of P?+?C vs. pembrolizumab monotherapy (P) is evaluated via an indirect treatment comparison, for patient subgroups with PD-L1 Tumor Proportion Score (TPS)?≥?50% and 1–49%.

Results: Overall, P?+?C is projected to increase life expectancy by 1.95?years vs. C (3.86 versus 1.91). The resultant ICER is $86,293/QALY. In patients with PD-L1?≥?50%, 1–49% and <1 the corresponding incremental cost-effectiveness ratios (ICERs) are $99,777/QALY, $85,986/QALY and $87,507/QALY, respectively. Versus P, in the PD-L1?≥?50% subgroup, P?+?C appears cost saving; however, this result should be interpreted with caution as there is considerable uncertainty in the relative efficacy of these comparators.

Conclusions: Across all eligible patients, the addition of pembrolizumab to chemotherapy is projected to approximately double life expectancy, yielding an extension to a point not previously seen in metastatic squamous NSCLC. Overall, and within all relevant PD-L1 subgroups, use of P?+?C yields an ICER below $100,000/QALY, and can be a cost-effective first-line treatment for eligible metastatic squamous NSCLC patients for whom chemotherapy is currently administered. In the PD-L1?≥?50% subgroup, additional follow-up within trials of pembrolizumab plus chemotherapy and pembrolizumab monotherapy are needed to better define cost-effectiveness between these comparators.     

Can scare tactics and fear-based messages help deter substance misuse: a systematic review of recent (2005–2017) research

Introduction: Historically, substance use prevention relied heavily on scare tactics and fear-based messages. However, these messages were discouraged from use due to research finding them ineffective or harmful. This review sought to determine if recent research continues to support this finding.

Methods: We conducted a literature review of relevant peer-reviewed studies from 2005 to 2017, categorising results as showing clear evidence of effectiveness, mixed evidence of effectiveness or no evidence of effectiveness. Research on historical scare tactics and fear-based messages was reviewed as a baseline and research on related theoretical models was reviewed for context.

Results: We identified 17 studies that met our inclusion criteria: 10 targeting tobacco use, five targeting alcohol use, one targeting marijuana use and one targeting methamphetamine use. Eight (8) studies found that these messages were more effective at influencing substance use-related measures than positive emotion prevention messages or control messages. Five (5) studies found mixed evidence, and four (4) studies found no evidence of effectiveness.

Discussion: Though not conclusive, our results suggest that these messages may be more effective than previously shown. However, many of the studied messages differed in tone and content from similar, historical messages. Organizations interested in implementing these messages should note these differences.     

Suicidal ideation and attempts among patients with lifetime physical and/or sexual abuse in treatment for substance use disorders

Background: Several studies indicate that lifetime abuse is a relevant risk factor for suicidal ideation and/or attempts. However, little is known about this phenomenon in patients seeking treatment for substance use disorder. The prevalence rate of suicidal ideation and/or suicide attempts was explored among lifetime physically and/or sexually abused patients receiving treatment for drug addiction. The differential characteristics between these patients and those without suicidal behaviours were studied.

Method: Three hundred and seventy-five patients were assessed. Socio-demographic characteristics, addiction severity, lifetime abuse, suicidal ideation and attempts, and psychopathological symptoms were explored.

Results: Eighty-two patients (21.9%) presented with a history of lifetime abuse and were included in the study (37 men and 45 women). Sixty-two per cent of them presented with lifetime suicidal ideation (12.2% in the last month), and 30.5% with suicide attempts (1.2% in the last month). Patients with suicidal ideation or attempts showed a more severe addiction profile (assessed by the EuropASI) and more psychopathological symptoms (assessed by the SCL-90-R).

Conclusion: This study highlights the relationship between previous traumatic experiences and suicidal behaviours. According to these results, systematic screening of suicidal risk in patients seeking treatment in addiction centres with histories of abuse is recommended.     

Evaluation of the amount of nanoparticles emitted in LASER additive manufacture/welding

Objectives: The objective of this study was the evaluation of the professional exposure to nanoparticles during tasks performed in workstations for production of metallic parts by laser welding additive manufacturing.

Materials and methods: The study was developed in an installed additive manufacturing machine, having controlled temperature and humidity in an industrial unit where metal parts were being produced using stainless steel powders of granulometry of 10 to 35?μm.

Results and discussion: Monitoring of airborne nanoparticles emission was made using adequate equipment, which showed considerable number of nanoparticles over the baseline, having the same composition as the steel powder used.

Conclusion: It is concluded that the values of professional exposure to nanoparticles are high in these workstations and that the nanoparticles to which the workers are exposed are small in size (around 15?nm), thus having a strong capacity for alveolar penetration and, consequently, with a strong possibility of passing to the bloodstream, accumulating in the body.     

Unraveling ‘The Cancer Genome Atlas’ information on the role of SLC transporters in anticancer drug uptake

Introduction: Anticancer chemotherapy often faces the problem of intrinsic or acquired drug refractoriness due in part to efficient mechanisms of defense present or developed, respectively, in cancer cells. Owing to their polarity and/or high molecular weight, many cytostatic agents cannot freely cross the plasma membrane by simple diffusion and hence depend on SLC proteins to enter cancer cells. The downregulation of these transporters and the appearance of either inactivating mutations or aberrant splicing, hamper the possibility of anticancer drugs to interact with their intracellular targets.

Areas covered: In addition to specific literature, we have revised Gene database of the NCBI PubMed resources and information publicly available at NIH ‘The Cancer Genome Atlas’ (TCGA) (update November 2018) to evaluate the relationship between the profile of expression of SLC transporters playing a major role in the transportome and accounting for drug uptake, in healthy and tumor tissue, and their ability to recognize as substrate several antitumor drugs frequently used in the treatment of different types of cancer, which could affect the overall response to chemotherapy based on regimens including these drugs.

Expert commentary: Changes in the transportome may affect the overall response to chemotherapy based on drugs taken up by SLC transporters.     

Safety of clinical practice guideline-recommended antiemetic agents for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric patients: a systematic review and meta-analysis

Introduction: Chemotherapy-induced nausea and vomiting (CINV) are among the most distressing and feared treatment-related adverse effects for cancer patients. Selection of antiemetic agents to prevent CINV should be based on an evaluation of their efficacy and safety. This systematic review and meta-analysis describes the adverse effects associated with antiemetic agents recommended for the prevention of acute CINV in children by clinical practice guidelines (CPGs).

Areas covered: A systematic literature search was conducted using four databases to identify papers describing adverse effects in pediatric patients receiving aprepitant, dexamethasone, granisetron, ondansetron, palonosetron, or tropisetron. Meta-analysis was conducted for adverse effects reported in at least three prospective studies with a cumulative incidence of at least 1%.

Expert opinion: Antiemetic agents currently recommended by CPGs are relatively safe to use in children. The presence of patient-specific risk factors for rare adverse effects, especially cardiac arrhythmia, should be evaluated when selecting a patient’s antiemetic therapy. Evaluation of the long-term safety of CPG-recommended antiemetic agents in pediatric cancer patients is needed.     

Emerging therapeutic strategies for transplantation-induced acute kidney injury: protecting the organelles and the vascular bed

Introduction: Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians in a broad variety of clinical settings such as perioperative and intensive care. Renal IRI induced acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs.

Areas covered: This paper focuses on the pathophysiology of transplantation-related AKI and recent findings on cellular stress responses at the intersection of 1. The Unfolded protein response; 2. Mitochondrial dysfunction; 3. The benefits of mineralocorticoid receptor antagonists. Lastly, perspectives are offered to the readers.

Expert opinion: Renal IRI is caused by a sudden and temporary impairment of blood flow to the organ.

Defining the underlying cellular cascades involved in IRI will assist us in the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer several advantages compared to targeting downstream inflammatory and fibrosis processes.

An improved understanding of the cellular pathophysiological mechanisms leading to kidney injury will hopefully offer improved targeted therapies to prevent and treat the injury in the future.