Helen Alderson

Extreme Elevations in Blood Pressure and All-Cause Mortality in a Referred CKD Population: Results from the CRISIS Study

Hypertension frequently complicates chronic kidney disease (CKD), with studies showing clinical benefit from blood pressure lowering. Subgroups of patients with severe hypertension exist. We aimed to identify patients with the greatest mortality risk from uncontrolled hypertension to define the prevalence and phenotype of patients who might benefit from adjunctive therapies. 1691 all-cause CKD patients from the CRISIS study were grouped by baseline blood pressure—target (<140/80 mmHg); elevated (140–190/80–100 mmHg); extreme (>190 and/or 100 mmHg). Groups were well matched for age, eGFR, and comorbidities. 77 patients had extreme hypertension at recruitment but no increased mortality risk (HR 0.9, P = 0.9) over a median follow-up period of 4.5 years. The 1.2% of patients with extreme hypertension at recruitment and at 12-months had a significantly increased mortality risk (HR 4.3, P = 0.01). This association was not seen in patients with baseline extreme hypertension and improved 12-month blood pressures (HR 0.86, P = 0.5). Most CKD patients with extreme hypertension respond to pharmacological blood pressure control, reducing their risk for death. Patients with extreme hypertension in whom blood pressure control cannot be achieved have an approximate prevalence of 1%. These patients have an increased mortality risk and may be an appropriate group to consider for further therapies, including renal nerve ablation.

Where now in the management of renal artery stenosis? Implications of the ASTRAL and CORAL trials.

Purpose of reviewThe neutral findings of Angioplasty and Stenting for Renal Artery Lesions and Cardiovascular Outcomes in Renal Artery Lesions trials have shown that unselected revascularization does not improve outcomes in atherosclerotic renovascular disease (ARVD). This review highlights recent translational, clinical and epidemiological studies and suggests directions for future research. Recent findingsImaging studies show that the degree of renal artery stenosis is not the most important determinant of outcome and response to therapies in ARVD. Porcine models have established a better understanding of the microvascular and inflammatory changes that occur in ARVD. Biomarkers of inflammation and cardiovascular dysfunction may be informative but do not yet help assess prognosis or response to treatment. Stem cell therapies show promise in animal models but have yet to translate into clinical practice. Analysis of patient subgroups with high-risk presentations of ARVD has provided new insights into treatment response and may guide future studies. SummaryIt is time to reframe thinking and research in ARVD. We need better ways to identify patients likely to benefit from revascularization and to improve response to treatment in these individuals. Many preclinical studies show promise, but these are often small scale and difficult to replicate. Future work should focus on establishing an international disease registry as a foundation for collaborative research.

Risks for mortality and renal replacement therapy in atherosclerotic renovascular disease compared to other causes of chronic kidney disease.

Patients with atherosclerotic renovascular disease (ARVD) have an increased risk for death and likelihood of initiating renal replacement therapy (RRT) compared with the general population. No data exist to describe prognosis in ARVD compared with other causes of chronic kidney disease (CKD). We compare patient outcomes between ARVD and other causes of CKD.

Functional status and mortality in chronic kidney disease: results from a prospective observational study

Background/Aims: Measures of functional status are used in the general population to aid prognostication but their use has not been explored in pre-dialysis chronic kidney disease (CKD). This analysis considers the association between the Karnofsky performance score (KPS) and all-cause mortality in a CKD stage 3-5 cohort. Methods: Patients were selected from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS), a prospective observational study of outcome in CKD. Risk for death was assessed using multivariate Cox regression, and differences in progression of biochemical parameters were considered in a mixed-effects model. Results: A total of 1,515 patients with a median follow-up time of 2.9 (1.5-4.8) years were considered. Baseline age was 60 ± 11 years and eGFR was 30 ± 12 ml/min/1.73 m2. Patients with a reduced KPS had an increased risk for death. The hazard ratio (HR) for death was: KPS 90 group, HR 1.2 (95% CI 0.9-1.5), p = 0.1; KPS ≤80 group, HR 1.8 (95% CI 1.4-2.4), p < 0.001. In the mixed-effects model, the average annual loss of eGFR was greater in patients with a KPS ≤80 versus patients with a KPS >80 (5 vs. 3%, p = 0.008). Conclusion: A reduced KPS is independently associated with risk for mortality in patients with CKD stages 3-5. This may relate to a more rapid loss of eGFR.

Potential for Biomarkers of Chronic Kidney Disease-Mineral Bone Disorder to Improve Patient Care

Chronic kidney disease (CKD) is a growing public health problem. Cardiovascular disease is common in CKD, but standard risk assessment tools perform poorly in this population. Equally, despite CKD being associated with an increased risk for death and dialysis, standard biochemical measurements have limited prognostic value. Novel serum biomarkers may aid risk assessment; however, studies have shown varying clinical utility in relation to progression of CKD, incident cardiovascular disease and death. This inconsistency may relate to limitations in our understanding of the biological actions and interactions of these biomarkers. This review discusses a range of biomarkers in relation to these clinical endpoints in CKD-mineral bone disorder. We consider where biomarkers may enhance risk stratification and improve clinical management, but also highlight where they fall short of achieving this objective.

An exploration of patients’ experiences of participation in a randomised controlled trial of the Manchester Acute Coronary Syndromes (MACS) decision rule

Background As an important part of a pilot study to determine the feasibility of a large randomised controlled trial (RCT) comparing use of the Manchester Acute Coronary Syndromes (MACS) decision rule with standard care, we aimed to explore patient attitudes and potential barriers to participation in a trial of this nature. Methods We conducted a qualitative study nested within a pilot RCT comparing use of the MACS rule (which could enable some patients with chest pain to be discharged earlier) with standard care. Semi-structured interviews with consenting participants were conducted with reference to a bespoke topic guide. Interviews were audio recorded, transcribed verbatim and analysed using the Framework method with an inductive approach. Results The 10 interviewees expressed that participation in the trial was generally acceptable. All but one recommended participation to others. Participants who were in pain or anxious at the time of arrival reported that the initial invitation to participate in the trial was sometimes made too early. The approach was welcome, providing they had been given time to settle. Interviewees welcomed the opportunity that trial participation offered for them to play a more active role in their healthcare and to reduce unnecessary waiting time. Participants appeared to like the fact that participation in the trial might mean they could return home sooner and welcomed the provision of follow-up. Although several participants described being generally sceptical of medical research, they were amenable to participation in this trial. This appears to be because they agreed with the need for research in this field and perceived the intervention as non-invasive. Conclusions Patients were positive about their participation in this RCT comparing the MACS rule with standard care. A number of areas for improving trial design were identified and should be considered in the planning of future large trials. Trial registration ISRCTN 86818215 Research ethics committee reference 13/NW/0081 UKCRN registration ID 14334