Clinical Applications of Remote Ischemic Preconditioning

Ischemia-reperfusion injury is a composite of damage accumulated during reduced perfusion of an organ or tissue and the additional insult sustained during reperfusion. Such injury occurs in a wide variety of clinically important syndromes, such as ischemic heart disease and stroke, which are responsible for a high degree of morbidity and mortality worldwide. Basic research has identified a number of interventions that stimulate innate resistance of tissues to ischemia-reperfusion injury. Here, we summarise the experimental and clinical trial data underpinning one of these “conditioning” strategies, the phenomenon of remote ischemic preconditioning

Clinical practice guidelines of remote ischemic conditioning for the management of cerebrovascular diseases

Remote ischemic conditioning (RIC) using transient limb ischemia and reperfusion has been shown in small clinical studies to reduce myocardial injury and infarction in cardiac patients, although larger clinical outcome studies have been neutral. Experimental and emerging clinical studies have also reported beneficial effects of limb RIC in a number of different settings of cerebrovascular disease including stroke (ischemic and hemorrhagic), carotid artery stenosis, intracranial artery stenosis, aneurysms, small vessel disease, and vascular cognitive impairment. Although limb RIC has many advantages, in that it is non-invasive, easy to administer, relatively innocuous, cost-effective, has few or no contraindications, and may be deployed under various circumstances (e.g., home, ambulance, and hospital), several questions remain regarding its clinical application for cerebrovascular disease. Therefore, in this document, we aim to provide practicing clinicians with a coherent synthesis of the latest scientific evidence, and we propose several recommendations to help facilitate the clinical application of limb RIC for the management of cerebrovascular disease

Patients’ and kidney care team’s perspectives of treatment burden and capacity in older people with chronic kidney disease: a qualitative study

Objective: Chronic kidney disease (CKD) is often a multimorbid condition and progression to more severe disease is commonly associated with increased management requirements, including lifestyle change, more medication, and greater clinician involvement. This study explored patients’ and kidney care team’s perspectives of the nature and extent of this workload (treatment burden) and factors that support capacity (the ability to manage health) for older individuals with CKD. Design: Qualitative semi-structured interview and focus group study Setting and Participants: Adults (aged 60+) with pre-dialysis CKD stages G3-5 (identified in two general practitioner surgeries and two renal clinics) and a multi-professional secondary kidney care team in the United Kingdom.Results: 29 individuals and 10 kidney team members were recruited. Treatment burden themes were: (a) understanding CKD, its treatment and consequences, (b) adhering to treatments and management, and (c) interacting with others (e.g.: clinicians) in the management of CKD. Capacity themes were: (a) personal attributes (e.g. optimism, pragmatism), (b) support network (family/friends, service providers), (c) financial capacity, environment (e.g.: geographical distance to unit) and life responsibilities (e.g.: caring for others). Patients reported poor provision of CKD information and lack of choice in treatment, whereas kidney care team members discussed health literacy issues. Patients reported having to withdraw from social activities and loss of employment due to CKD, which further impacted their capacity. Conclusion: Improved understanding of and measures to reduce the treatment burden (e.g. clear information, simplified medication, joined up care, free parking) associated with CKD in individuals as well as assessment of their capacity and interventions to improve capacity (social care, psychological support) will likely improve patient experience and their engagement with kidney care services

Early changes in scores of chronic damage on transplant kidney protocol biopsies reflect donor characteristics, but not future graft function.

The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single-center cohort, we examined the relationship between donor-, recipient-, and transplantation-associated factors and change in a morphometric index of chronic damage (ICD) between protocol biopsies performed at implantation and at 2-3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0-8) and 2-3 months post-transplant (median 8% IQR:4-15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post-transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes

Patients’ and kidney care team’s perspectives of treatment burden and capacity in older people with chronic kidney disease: a qualitative study

Objective Chronic kidney disease (CKD) is often a multimorbid condition and progression to more severe disease is commonly associated with increased management requirements, including lifestyle change, more medication and greater clinician involvement. This study explored patients’ and kidney care team’s perspectives of the nature and extent of this workload (treatment burden) and factors that support capacity (the ability to manage health) for older individuals with CKD.Design Qualitative semistructured interview and focus group study.Setting and participants Adults (aged 60+) with predialysis CKD stages G3–5 (identified in two general practitioner surgeries and two renal clinics) and a multiprofessional secondary kidney care team in the UK.Results 29 individuals and 10 kidney team members were recruited. Treatment burden themes were: (1) understanding CKD, its treatment and consequences, (2) adhering to treatments and management and (3) interacting with others (eg, clinicians) in the management of CKD. Capacity themes were: (1) personal attributes (eg, optimism, pragmatism), (2) support network (family/friends, service providers), (3) financial capacity, environment (eg, geographical distance to unit) and life responsibilities (eg, caring for others). Patients reported poor provision of CKD information and lack of choice in treatment, whereas kidney care team members discussed health literacy issues. Patients reported having to withdraw from social activities and loss of employment due to CKD, which further impacted their capacity.Conclusion Improved understanding of and measures to reduce the treatment burden (eg, clear information, simplified medication, joined up care, free parking) associated with CKD in individuals as well as assessment of their capacity and interventions to improve capacity (social care, psychological support) will likely improve patient experience and their engagement with kidney care services

A role for genetic modifiers in tubulointerstitial kidney diseases

With the increased availability of genomic sequencing technologies, the molecular bases for kidney diseases such as nephronophthisis and mitochondrially inherited and autosomal-dominant tubulointerstitial kidney diseases (ADTKD) has become increasingly apparent. These tubulointerstitial kidney diseases (TKD) are monogenic diseases of the tubulointerstitium and result in interstitial fibrosis and tubular atrophy (IF/TA). However, monogenic inheritance alone does not adequately explain the highly variable onset of kidney failure and extra-renal manifestations. Phenotypes vary considerably between individuals harbouring the same pathogenic variant in the same putative monogenic gene, even within families sharing common environmental factors. While the extreme end of the disease spectrum may have dramatic syndromic manifestations typically diagnosed in childhood, many patients present a more subtle phenotype with little to differentiate them from many other common forms of non-proteinuric chronic kidney disease (CKD). This review summarises the expanding repertoire of genes underpinning TKD and their known phenotypic manifestations. Furthermore, we collate the growing evidence for a role of modifier genes and discuss the extent to which these data bridge the historical gap between apparently rare monogenic TKD and polygenic non-proteinuric CKD (excluding polycystic kidney disease)

A Role for Genetic Modifiers in Tubulointerstitial Kidney Diseases

With the increased availability of genomic sequencing technologies, the molecular bases for kidney diseases such as nephronophthisis and mitochondrially inherited and autosomal-dominant tubulointerstitial kidney diseases (ADTKD) has become increasingly apparent. These tubulointerstitial kidney diseases (TKD) are monogenic diseases of the tubulointerstitium and result in interstitial fibrosis and tubular atrophy (IF/TA). However, monogenic inheritance alone does not adequately explain the highly variable onset of kidney failure and extra-renal manifestations. Phenotypes vary considerably between individuals harbouring the same pathogenic variant in the same putative monogenic gene, even within families sharing common environmental factors. While the extreme end of the disease spectrum may have dramatic syndromic manifestations typically diagnosed in childhood, many patients present a more subtle phenotype with little to differentiate them from many other common forms of non-proteinuric chronic kidney disease (CKD). This review summarises the expanding repertoire of genes underpinning TKD and their known phenotypic manifestations. Furthermore, we collate the growing evidence for a role of modifier genes and discuss the extent to which these data bridge the historical gap between apparently rare monogenic TKD and polygenic non-proteinuric CKD (excluding polycystic kidney disease)

Acute kidney injury in COVID‐19: Identification of risk factors and potential biomarkers of disease in a large UK cohort

BackgroundCOVID‐19 is associated with increased risk of acute kidney injury (AKI). Risk factors and biomarkers linked to AKI have now been recognized by national guidelines in the United Kingdom. This analysis aims to validate and expand the comorbidities and biomarkers associated with the presence and severity of AKI in these patients.MethodsData were extracted via structured query language for patients with COVID‐19 at University Hospital Southampton between 1 March and 10 June 2020. Demographics, comorbidities, common biomarkers and AKI stage within 48 hours of admission, peak during admission and the last measurement prior to patient outcome (discharge or death) were collected and statistically analysed.ResultsSix hundred and thirty‐two COVID‐19 positive patients were admitted during this period; 34.2% had an AKI during their entire admission, 20.3% had AKI stage 1, 8.5% stage 2 and 5.4% stage 3. This was higher when compared with data from the same period in 2019. AKI carried an increased risk of death, 50.0% vs 21.1% (P = &lt;.001). AKI stage was significantly associated with age over 65, diabetes, heart failure, peripheral vascular disease, haematological malignancy, hypertension, respiratory rate, albumin, C‐reactive protein (CRP), d‐dimer, ferritin, high‐sensitivity troponin‐I, neutrophil count, total white cell counts, National Early Warning Score‐2 (NEWS‐2), Charlson comorbidity index and alanine‐aminotransferase. COVID‐19 specific treatment, including dexamethasone, reduced discharge creatinine.ConclusionCOVID‐19 increases the risk of AKI and this kidney injury may be responsive to treatment. This analysis identified that AKI is associated with both previously described and new comorbidities and biomarkers.</p