The global shortage of suitable donor kidneys is the primary challenge in kidney transplantation, and it is exacerbated by ageing donors with increased numbers of health issues. Improving organ assessment, preservation and conditioning could enhance organ utilization and patient outcomes. Hypothermic machine perfusion (HMP) is associated with better results than static cold storage by reducing delayed graft function and improving short-term graft survival, especially in kidneys recovered from marginal-quality donors. Although HMP is useful for organ preservation, it is difficult to assess organ viability during HMP because of the reduced metabolic activity at low temperatures, and the adoption of HMP has faced logistical challenges. The addition of oxygen during HMP is aimed at reducing ischaemia-reperfusion injury, but has shown mixed results in kidney transplantation, often depending on the duration of perfusion, although some studies found that the addition of oxygen improved outcomes in higher-risk donors. Normothermic machine perfusion helps to restore kidney function by delivering oxygen and nutrients at body temperature, potentially reducing ischaemia-reperfusion injury. Early studies suggest its safety, but clinical benefits remain unproven. Normothermic machine perfusion also holds promise for assessing organ viability pre-transplantation by enabling real-time evaluation. In this Review, we will summarize the different methods of kidney preservation, providing details of the effect that each method has on graft and patient outcomes and the strengths and limitations of each method.
\n \n\n \n \nOBJECTIVE: Fibrosis is a pathological feature that can occur in a wide range of diseases including diabetes mellitus. We investigated whether in people with type 1 (T1DM) or type 2 diabetes mellitus (T2DM), glycaemia or diabetes-related complications are associated with fibrotic diseases. DESIGN AND SETTING: Retrospective cohort study using UK Clinical Resource Datalink (CPRD) Aurum and Hospital Episode Statistics. PARTICIPANTS: We included people with prevalent T1DM or T2DM as of 31 December 2015 (recorded in CPRD Aurum), eligible for linkage with Hospital Episode Statistics and followed up for 3 years. OUTCOME MEASURES: We defined diabetes status using blood/urine biomarkers and complications. In the T2DM cohort, we also investigated exposures of hyperglycaemia, insulin resistance and metformin prescription. Fibrotic condition diagnoses were determined from both primary and secondary care records. Logistic regression analyses were undertaken to understand the strength of association between diabetes status/diabetic complications and fibrotic conditions, respectively. RESULTS: The T1DM cohort consisted of 9669 people while the T2DM cohort included 504\u2009066 people. In T1DM, we found that albuminuria was associated with lung fibrosis (ORadj: 2.07, 99%\u2009CI 1.35 to 2.17), and microvascular complications were associated with atherosclerosis (ORadj: 1.81, 99%\u2009CI 1.18 to 2.77) and cardiomyopathy (ORadj 1.53, 99%\u2009CI:1.15 to 2.04). In the T2DM cohort, both glycaemia above target and diabetes complications were associated with most fibrotic conditions. CONCLUSIONS: Within the T1DM population, no consistent association between diabetes status and all fibrotic diseases was observed. More research is required to understand whether the association between diabetes complications and fibrotic diseases is due to shared risk factors or whether glycaemia in T2DM may be influenced by fibrotic pathology.
\n \n\n \n \nBACKGROUND: Multimorbidity has been identified as a research priority in recent years, fibrosis (progressive organ scarring) is one mechanism which may underpin multimorbidity. Some studies suggest hypertension could be fibrotic, particularly severe hypertension (uncontrollable with medications), however it is not currently known whether severe hypertension is associated with fibrotic conditions. OBJECTIVE: To investigate whether treatment resistant hypertension is associated with fibrotic conditions. METHODS: We used the Clinical Practice Research Datalink (CPRD) Aurum primary care database to define a cohort of people with hypertension during 2015. We determined the percentage of people who had conditions with fibrotic manifestations and explored differences respective to hypertension control. We applied multivariable logistic regression to analyse associations (p<0.001) between hypertension control and each fibrotic condition respectively. RESULTS: Of 1,340,495 people with hypertension during 2015, 83.50% (n=1,119,333) had managed hypertension either by lifestyle or medication; 16.50% (n=221,162) had treatment resistant hypertension. Fibrotic conditions were more common ((75.40% (95%CI: 75.20-75.60) vs. 68.90% (95%CI: 68.81-70.01)) in people with treatment resistant hypertension compared with those with managed hypertension. We found that treatment resistant hypertension was associated with; cardiomyopathy (ORadj:1.85, 95%CI:1.81-1.90), both type 1 and type 2 diabetes (ORadj:1.49,95%CI:1.44-1.55, ORadj:1.61,95%CI:1.60-1.63, respectively), liver fibrosis (ORadj:1.52, 95%CI: 1.46-1.58), valve fibrosis (ORadj:1.41, 95%CI:1.37-1.44) and urinary fibrosis (ORadj:1.41,95%CI:1.36-1.47). CONCLUSION: The proportion of people with fibrotic conditions was greater in those with treatment resistant hypertension than managed hypertension. The identified associations between treatment resistant hypertension and fibrotic conditions may point to common disease pathways which should be further explored to understand shared mechanisms.
\n \n\n \n \nBACKGROUND: Electronic healthcare records (EHRs) are used to document diagnoses, symptoms, tests, and prescriptions. Though not primarily collected for research purposes, owing to the size of the data as well as the depth of information collected, they have been used extensively to conduct epidemiological research. The Clinical Practice Research Datalink (CPRD) is an EHR database containing representative data of the UK population with regard to age, sex, race, and social deprivation measures. Fibrotic conditions are characterised by excessive scarring, contributing towards organ dysfunction and eventual organ failure. Fibrosis is associated with ageing as well as many other factors, it is hypothesised that fibrotic conditions are caused by the same underlying pathological mechanism. We calculated the prevalence of fibrotic conditions (as defined in a previous Delphi survey of clinicians) as well as the prevalence of fibrotic multimorbidity (the proportion of people with multiple fibrotic conditions). METHODS: We included a random sample of 993,370 UK adults, alive, and enrolled at a UK general practice, providing data to the CPRD Aurum database as of 1st of January 2015. Individuals had to be eligible for linkage to hospital episode statistics (HES) and ONS death registration. We calculated the point prevalence of fibrotic conditions and multi-morbid fibrosis on the 1st of January 2015. Using death records of those who died in 2015, we investigated the prevalence of fibrosis associated death. We explored the most commonly co-occurring fibrotic conditions and determined the settings in which diagnoses were commonly made (primary care, secondary care or after death). RESULTS: The point prevalence of any fibrotic condition was 21.46%. In total, 6.00% of people had fibrotic multimorbidity. Of the people who died in 2015, 34.82% had a recording of a fibrotic condition listed on their death certificate. CONCLUSION: The key finding was that fibrotic multimorbidity affects approximately 1 in 16 people.
\n \n\n \n \nBACKGROUND AND AIMS: Hypertension is a leading risk factor for cardiovascular disease. Electronic health records (EHRs) are routinely collected throughout a person's care, recording all aspects of health status, including current and past conditions, prescriptions and test results. EHRs can be used for epidemiological research. However, there are nuances in the way conditions are recorded using clinical coding; it is important to understand the methods which have been applied to define exposures, covariates and outcomes to enable interpretation of study findings. This study aimed to identify codelists used to define hypertension in studies that use EHRs and generate recommended codelists to support reproducibility and consistency. ELIGIBILITY CRITERIA: Studies included populations with hypertension defined within an EHR between January 2010 and August 2023 and were systematically identified using MEDLINE and Embase. A summary of the most frequently used sources and codes is described. Due to an absence of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) codelists in the literature, a recommended SNOMED CT codelist was developed to aid consistency and standardisation of hypertension research using EHRs. FINDINGS: 375 manuscripts met the study criteria and were eligible for inclusion, and 112 (29.9%) reported codelists. The International Classification of Diseases (ICD) was the most frequently used clinical terminology, 59 manuscripts provided ICD 9 codelists (53%) and 58 included ICD 10 codelists (52%). Informed by commonly used ICD and Read codes, usage recommendations were made. We derived SNOMED CT codelists informed by National Institute for Health and Care Excellence guidelines for hypertension management. It is recommended that these codelists be used to identify hypertension in EHRs using SNOMED CT codes. CONCLUSIONS: Less than one-third of hypertension studies using EHRs included their codelists. Transparent methodology for codelist creation is essential for replication and will aid interpretation of study findings. We created SNOMED CT codelists to support and standardise hypertension definitions in EHR studies.
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