The effect of a novel, digital physical activity and emotional well-being intervention on health-related quality of life in people with chronic kidney disease: trial design and baseline data from a multicentre prospective, wait-list randomised controlled trial (kidney BEAM).

BACKGROUND: Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. METHODS: This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. RESULTS: 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. CONCLUSION: Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. TRIAL REGISTRATION: NCT04872933. Registered 5th May 2021.

Symptom-burden in people living with frailty and chronic kidney disease.

BACKGROUND: Frailty is independently associated with worse health-related quality of life (HRQOL) in chronic kidney disease (CKD). However, the relationship between frailty and symptom experience is not well described in people living with CKD. This study's aim was to evaluate the relationship between frailty and symptom-burden in CKD. METHODS: This study is a secondary analysis of a cross-sectional observational study, the QCKD study (ISRCTN87066351), in which participants completed physical activity, cardiopulmonary fitness, symptom-burden and HRQOL questionnaires. A modified version of the Frailty Phenotype, comprising 3 self-report components, was created to assess frailty status. Multiple linear regression was performed to assess the association between symptom-burden/HRQOL and frailty. Logistic regression was performed to assess the association between experiencing symptoms frequently and frailty. Principal Component Analysis was used to assess the experienced symptom clusters. RESULTS: A total of 353 patients with CKD were recruited with 225 (64%) participants categorised as frail. Frail participants reported more symptoms, had higher symptom scores and worse HRQOL scores. Frailty was independently associated with higher total symptom score and lower HRQOL scores. Frailty was also independently associated with higher odds of frequently experiencing 9 out of 12 reported symptoms. Finally, frail participants experienced an additional symptom cluster that included loss of appetite, tiredness, feeling cold and poor concentration. CONCLUSIONS: Frailty is independently associated with high symptom-burden and poor HRQOL in CKD. Moreover, people living with frailty and CKD have a distinctive symptom experience. Proactive interventions are needed that can effectively identify and address problematic symptoms to mitigate their impact on HRQOL.

The epidemiology of hospitalised acute kidney injury not requiring dialysis in England from 1998 to 2013: retrospective analysis of hospital episode statistics.

AIMS: Epidemiology studies of acute kidney injury (AKI) have focused on cases requiring dialysis but those not requiring dialysis represent the majority. To address this gap, we interrogated hospital episode statistics (HES) to investigate population trends in temporal epidemiology of AKI not requiring dialysis between 1998 and 2013. METHODOLOGY: In this retrospective observational study of HES data covering the entire English National Health Service, we identified 1,136,167 AKI events, not requiring dialysis, diagnosed between 1998 and 2013. We explored the effect of age, gender, ethnicity, Charlson's comorbidity score (CCS), method of admission, diagnosis period and AKI in diagnosis codes on temporal changes in the incidence and case-fatality of AKI with specific examination of its predictors. RESULT: The incidence of AKI increased from 15,463 cases (317 pmp) in 1998-1999 to 213,700 cases (3995 pmp) in 2012-2013. There was increase in proportion of people over 75 years from 51.1% in 1998-1999 to 63.4% in 2012-2013. Overall unadjusted case-fatality decreased from 42.3% in 1998-2003 to 27.1% in 2008-2013, p < 0.001. Compared with 1998-2003, the multivariable adjusted odds ratio for death was 0.64 in 2003-2008 (95% CI 0.63-0.65) and 0.35 in 2008-2013 (95% CI 0.34-0.35). Odds for death were higher for patients over 85 years (2.93; 95% CI 2.89-2.97), CCS of more than five (2.75; 95% CI 2.71-2.79), emergency admissions (2.14; 95% CI 2.09-2.18) and AKI in the secondary diagnosis code (1.35; 95% CI 1.33-1.36) and AKI in other diagnoses codes (2.17; 95% CI 2.15-2.20). CONCLUSIONS: In England, the incidence of AKI not requiring dialysis has increased and case-fatality has decreased over last 15 years. Efforts to reduce the incidence of AKI and improve survival should focus on elderly people, emergency admissions and those with multi-morbidity.

Renal risk scores: progress and prospects.

Worldwide adoption of the Kidney Disease Outcomes Quality Initiative classification for chronic kidney disease (CKD) and widespread use of the estimated glomerular filtration rate to assess renal function have identified large numbers of patients with previously undiagnosed CKD. It is clear, however, that this is a heterogeneous group and that only a small minority of such patients ever progress to end-stage renal disease. There is thus an urgent need for a simple method of risk assessment that can be applied to all patients with CKD to identify those few at greatest risk. The magnitude of baseline proteinuria has long been recognized as an important predictor of renal prognosis. Furthermore, several studies have found that change in proteinuria after initiation of antihypertensive treatment as well as achieved level of proteinuria correlate with prognosis. Thus, proteinuria has emerged as the single most important marker of renal risk. Many other factors have been identified as risk factors for CKD progression. Several attempts have been made to combine a relatively small number of risk factors into a risk score to predict renal outcomes in specific groups of patients. Validation of these risk scores as well as further studies are now required to develop a renal risk score applicable to a more general population of patients with CKD. Similar methodology could be applied to assess the important issue of the cardiovascular risk associated with CKD.

Hepatitis E virus infection and acute-on-chronic liver failure in West Africa: a case-control study from The Gambia.

BACKGROUND: In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF). AIMS: To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa. METHODS: We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls. RESULTS: In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), ≥70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality. CONCLUSIONS: Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia.

Activation of the heart by donor brain death accelerates acute rejection after transplantation.

BACKGROUND: Donor brain death upregulates expression of inflammatory mediators in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts from normal living donors. We examined the inflammatory and immunological consequences of gradual-onset donor brain death on cardiac allografts after transplantation. METHODS AND RESULTS: Functioning hearts were engrafted from normotensive donors after 6 hours of ventilatory support. Hearts from brain-dead rats (Fisher, F344) were rejected significantly earlier (mean+/-SD, 9. 3+/-0.6 days) by their (Lewis) recipients than hearts from living donor controls (11.6+/-0.7 days, P=0.03). The inflammatory response of such organs was accelerated, with rapid expression of cytokines, chemokines, and adhesion molecules and brisk infiltration of associated leukocyte populations. Upregulation of major histocompatibility class II antigens increased organ immunogenicity. Acute rejection evolved in hearts from brain-dead donors more intensely and at a significantly faster rate than in controls. CONCLUSIONS: Donor brain death is deleterious to transplanted hearts. The resultant upregulation of inflammatory factors provokes host immune mechanisms and accelerates the acute rejection process in unmodified hosts.

High sodium intake is associated with important risk factors in a large cohort of chronic kidney disease patients.

BACKGROUND/OBJECTIVES: An increased risk of mortality and cardiovascular disease (CVD) is observed in people with chronic kidney disease (CKD) even in early stages. Dietary sodium intake has been associated with important CVD and CKD progression risk factors such as hypertension and proteinuria in this population. We aimed to investigate the relationship between sodium intake and CVD or CKD progression risk factors in a large cohort of patients with CKD stage 3 recruited from primary care. SUBJECTS/METHODS: A total of 1733 patients with previous estimated glomerular filtration rate (eGFR) of 30-59 ml/min/1.73m(2), with a mean age 72.9±9.0 years, were recruited from 32 general practices in primary care in England. Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Sodium intake was estimated from three early-morning urine specimens using an equation validated for this study population. RESULTS: Sixty percent of participants who had estimated sodium intake above recommendation (>100 mmol/day or 6 g salt/day) also had higher diastolic blood pressure, mean arterial pressure (MAP), urinary albumin-to-creatinine ratio, high-sensitive C-reactive protein and uric acid and used a greater number of anti-hypertensive drugs. In multivariable regression analysis, excessive sodium intake was an independent predictor of MAP (B=1.57, 95% confidence interval (CI) 0.41-2.72; P=0.008) and albuminuria (B=1.35, 95% CI 1.02-1.79; P=0.03). CONCLUSIONS: High sodium intake was associated with CVD and CKD progression risk factors in patients with predominantly early stages of CKD followed up in primary care. This suggests that dietary sodium intake could afffect CVD risk even in early or mild CKD. Intervention studies are warranted to investigate the potential benefit of dietary advice to reduce sodium intake in this population.

Achieving maximal renal protection in nondiabetic chronic renal disease.

A rapid global increase in the number of patients requiring renal replacement therapy necessitates that effective strategies for renal protection are developed and applied widely. We review the experimental and clinical evidence in support of individual renoprotective interventions, including angiotensin-converting enzyme therapy, control of systemic hypertension, dietary protein restriction, reduction of proteinuria, treatment of hyperlipidemia, and smoking cessation. We also consider potential future renoprotective therapies. To achieve maximal renal protection, a comprehensive strategy employing all of these elements is required. This strategy should be directed at normalizing clinical markers of renal disease to induce a state of remission.

ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in chronic rat models.

There is now abundant evidence that treatment with angiotensin-converting enzyme inhibitors (ACE-I) ameliorates the progression of chronic renal disease. Attention has therefore focused on the role of the renin angiotensin-aldosterone (RAA) system in mediating the development of progressive glomerulosclerosis and angiotensin II (Ang II) has been implicated in several processes thought to be important in the pathogenesis of this entity. Conversely, ACE is also known to catalyse the breakdown of bradykinin. Thus, ACE-I treatment results in elevated bradykinin levels which may cause selective efferent arteriolar dilatation, suggesting an alternative explanation for the beneficial effects of this class of drugs in chronic renal disease. The development of specific angiotensin type 1 receptor antagonists (AT1RA) has provided a means of testing the relative importance of these two mechanisms. In addition, AT1RAs differ from ACE-I in their effect on the RAA system in other aspects which may represent therapeutic advantages. This paper reviews studies which have compared ACE-I and AT1RAs in several rat models of chronic renal disease. Most have found similar beneficial effects including amelioration of proteinuria and glomerulosclerosis, which suggests that the effects of ACE-I are due to a reduction in Ang II activity and not due to increased levels of bradykinin. One long-term study has suggested greater renal protection with candesartan than with enalapril. However, conclusions as regards the relative efficacy of these two groups of agents in ameliorating the progression of chronic renal disease await the results of further long-term studies.

Positive and negative effects of a child sexual abuse prevention program.

This study evaluated a sexual abuse prevention program for sixth, seventh, and eighth graders ranging from 8 to 12 years of age. Six questionnaires concerning feelings of control, choice of protection strategy, perceived feasibility of refusing to cooperate with the intruder, appreciation of touch, school relationships, and social anxiety were used. Subjects were 161 children who participated in the program and a control group of 131 children. Results indicated short term overall effects of the program for the choice of safety strategies. Immediately after participation in the program the youngest and the oldest children felt less in control of an abusive interaction, the youngest pupils thought that refusal was less feasible but they appreciated physical touch more than before. These effects, however, were only of a short duration. In the long run children thought refusing more feasible and younger children showed less social anxiousness. As an unwanted side effect of the program the oldest children developed feelings of discomfort about being touched. Relationships with classmates and the teacher were not influenced by the intervention. It is suggested that the behavioral and attitudinal effects of the program could be ameliorated by extending the number or duration of the lessons.

Food intake increases liver stiffness measurements and hampers reliable values in patients with chronic hepatitis B and healthy controls: the PROLIFICA experience in The Gambia.

BACKGROUND: By increasing the hepatic blood circulation, food intake has been suggested to increase liver stiffness measurement (LSM) values in HCV-infected patients. AIM: To investigate prospectively the effects of food intake on LSM in hepatitis B virus (HBV)-infected patients and healthy controls. METHODS: In The Gambia, patients included in the PROLIFICA project are screened for HBV at the community level and then invited for fasting assessment including LSM. Between April 2012 and October 2012, each day, the first five participants were invited to participate in this study. After the initial examination, a standardised 850 Kcal breakfast was provided. Effect of food intake was assessed by examining mean difference of LSM, IQR and IQR/LSM at T0 (fasting LSM1), T30min (LSM2) and T120min (LSM3) respectively. RESULTS: A total of 209 subjects were enrolled in this study (133 were HBV positive, 76 healthy controls). Unreliable measurements occurred more frequently after food intake (5%, 24% and 18% at T0, T30min and T120min respectively). In both groups, median LSM2 was significantly higher than LSM1 [6.2 (IQR: 5.4, 7.9)] vs. 4.9 (4.2, 6.2), P < 0.0001. LSM3 was still higher than the baseline, but lower than LSM2. In multivariable analysis, no factor modified the effect of breakfast on LSM. In a subgroup of patients having liver biopsies, we confirmed that food intake can overestimate liver fibrosis. CONCLUSIONS: Food intake significantly increases liver stiffness measurement and its IQR values in patients with chronic hepatitis B as well as healthy individuals; and also the number of unreliable liver stiffness measurement values.

Predicting initiation and progression of chronic kidney disease: Developing renal risk scores.

Epidemiological studies have raised awareness of the problem of undiagnosed chronic kidney disease (CKD) and suggest that early identification and treatment will reduce the global burden of patients requiring dialysis. This has highlighted the twin problems of how to identify subjects for screening and target intervention to those with CKD most likely to progress to end-stage renal disease. Prospective studies have identified risk factors for CKD in the general population as well as risk factors for progression in patients with established CKD. Risk factors may thus be divided into initiating factors and perpetuating factors, with some overlap between the groups. In this paper, we review current data regarding CKD risk factors and illustrate how each may impact upon the mechanisms underlying CKD progression to accelerate loss of renal function. We propose that these risk factors should be used as a basis for developing a renal risk score, analogous to the Framingham risk score for ischemic heart disease, which will allow accurate determination of renal risk in the general population and among CKD patients.

Angiotensin-converting enzyme gene polymorphisms in renal disease: clinically relevant?

The most recent studies of the effect of polymorphisms of the angiotensin-converting enzyme gene on the pathogenesis of renal diseases and the response to treatment with angiotensin-converting enzyme inhibitors continue to produce conflicting results. Large prospective studies are required before angiotensin-converting enzyme genotyping will provide information that will assist in the assessment of prognosis and response to angiotensin-converting enzyme inhibitor treatment in individual patients. Until such studies are performed, all patients with chronic renal disease, regardless of angiotensin-converting enzyme genotype, should be considered candidates for angiotensin-converting enzyme inhibitor therapy.

Stimulating adolescents' decision-making.

The aim of the present study was to investigate the relationship between adolescents' decision-making and their sense of control over the future. In order to raise their knowledge of decision-making, 98 lower-middle class junior high school pupils, 11- to 14-years-olds, participated in a training programme "Pros and Cons". The programme presented themes such as responsibility, plans, choice and alternatives. The experimental group was compared with 122 junior high school pupils who did not participate in the programme, within a quasi-experimental design. Results of the study indicated that increased knowledge of decision-making raises pupils' sense of control over their achievements and their perception of school as an instrument for their future career.

Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists.

In landmark clinical trials, pharmacological inhibition of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) attenuated the decline in renal function associated with chronic renal disease (CRD). Hemodynamic and nonhemodynamic effects of angiotensin II (Ang II) attest to its central role in the pathogenesis of CRD. Angiotensin II subtype 1 receptor antagonists (AT1RA) differ from ACEI in their effects on the RAS and on bradykinin metabolism. Elevations in bradykinin levels associated with ACEI and stimulation of angiotensin subtype 2 receptors resulting from AT1RA may produce therapeutic effects unique to each class of drug. Nevertheless, in animal models of CRD, ACEI and AT1RA exert equivalent renoprotection, implying that their renoprotective effects result primarily from inhibition of Ang II-mediated stimulation of angiotensin subtype 1 receptors. Clinical data comparing ACEI and AT1RA therapy in renal disease are limited to short-term studies, which indicate that AT1RAs have equivalent effects to ACEI on the major determinants of CRD progression, namely blood pressure and proteinuria. AT1RAs were well tolerated, with side-effect profiles similar to placebo. Taken together, available evidence suggests that AT1RAs will share the renoprotective properties of ACEI in human CRD. Nevertheless, the results of long-term clinical trials are required before AT1RA can be recommended as an alternative to ACEI in renoprotective therapy.

Evolving strategies for renoprotection: non-diabetic chronic renal disease.

Experimental and clinical studies over the past two decades have identified several interventions for slowing the progression of chronic renal disease towards end-stage renal failure. In this paper we review the experimental and clinical evidence in support of dietary protein restriction, angiotensin-converting enzyme inhibitor therapy, control of systemic hypertension, reduction of proteinuria, treatment of hyperlipidemia and smoking cessation. We also consider potential future renoprotective therapies. Finally we propose a comprehensive strategy for achieving maximal renoprotection with available interventions and monitoring.

Cost-effectiveness of hepatitis B vaccination in haemodialysis patients.

BACKGROUND: Vaccination against hepatitis B virus is an important means of controlling the infection, but its role in haemodialysis patients has been questioned due to the latter's impaired immune response. METHODS: Forty-eight of 79 haemodialysis patients who were negative for antibodies to both hepatitis B surface and core antigens were entered into a vaccination programme. Standard doses of a plasma-derived vaccine were administered into the deltoid muscle at 0, 1, 2 and 4 months, and the antibody response was measured at 1 and 2 months after the third and fourth doses. RESULTS: The peak mean antibody titre of 372 IU/l was recorded at 1 month after the fourth dose, and the maximum response rate was achieved at 2 months after the final dose. Seroconversion occurred in 26 of 36 patients (72%) who completed the programme, and protective levels of antibody above 10 IU/l were found in 25 of 36 patients (69%). Cost analysis of the project revealed a net saving of +/- R90/patient entered at the end of the first year, due to the reduced number of patients requiring monthly surveillance tests for hepatitis B surface antigen. After that, an annual saving of +/- R380/patient is projected. CONCLUSION: In view of the high prevalence of chronic hepatitis B carriers in the South African population, the reduction in the number of patients at risk of infection, combined with a net cost saving, makes it reasonable to recommend vaccination in all non-immune haemodialysis patients despite a reduced response rate.