Treatment options for primary IgA nephropathy (IgAN) and Henoch-Schönlein nephritis are still largely based on opinion or weak evidence. Consequently, the recent KDIGO Clinical Practice Guidelines ...for Glomerulonephritis have assigned low levels of evidence for almost all recommendations and suggestions related to these two diseases. In this Review, we describe an algorithm for structuring the treatment of IgAN depending on the clinical scenario. Key to therapeutic decision making is assessment of the individual's prognosis. Clinical parameters (such as proteinuria, hypertension, and impaired glomerular filtration rate GFR) are used to estimate risk, but the clinical value of the novel histological Oxford-MEST classification remains to be determined. If these parameters indicate a risk of progressive GFR loss, comprehensive supportive care remains the mainstay of therapy. Two large trials, STOP-IgAN and TESTING, are underway to evaluate the value of adding corticosteroids after initiating such supportive care. At present, little evidence exists to suggest that any other immunosuppressive therapy beyond corticosteroids is effective in either IgAN or Henoch-Schönlein nephritis.
Summary Background Membranous nephropathy leads to end-stage renal disease in more than 20% of patients. Although immunosuppressive therapy benefits some patients, trial evidence for the subset of ...patients with declining renal function is not available. We aimed to assess whether immunosuppression preserves renal function in patients with idiopathic membranous nephropathy with declining renal function. Methods This randomised controlled trial was undertaken in 37 renal units across the UK. We recruited patients (18–75 years) with biopsy-proven idiopathic membranous nephropathy, a plasma creatinine concentration of less than 300 μmol/L, and at least a 20% decline in excretory renal function measured in the 2 years before study entry, based on at least three measurements over a period of 3 months or longer. Patients were randomly assigned (1:1:1) by a random number table to receive supportive treatment only, supportive treatment plus 6 months of alternating cycles of prednisolone and chlorambucil, or supportive treatment plus 12 months of ciclosporin. The primary outcome was a further 20% decline in renal function from baseline, analysed by intention to treat. The trial is registered as an International Standard Randomised Controlled Trial, number 99959692. Findings We randomly assigned 108 patients, 33 of whom received prednisolone and chlorambucil, 37 ciclosporin, and 38 supportive therapy alone. Two patients (one who received ciclosporin and one who received supportive therapy) were ineligible, so were not included in the intention-to-treat analysis, and 45 patients deviated from protocol before study end, mostly as a result of minor dose adjustments. Follow up was until primary endpoint or for minimum of 3 years if primary endpoint was not reached. Risk of further 20% decline in renal function was significantly lower in the prednisolone and chlorambucil group than in the supportive care group (19 58% of 33 patients reached endpoint vs 31 84% of 37, hazard ratio HR 0·44 95% CI 0·24–0·78; p=0·0042); risk did not differ between the ciclosporin (29 81% of 36) and supportive treatment only groups (HR 1·17 0·70–1·95; p=0·54), but did differ significantly across all three groups (p=0·003). Serious adverse events were frequent in all three groups but were higher in the prednisolone and chlorambucil group than in the supportive care only group (56 events vs 24 events; p=0·048). Interpretation For the subset of patients with idiopathic membranous nephropathy and deteriorating excretory renal function, 6 months' therapy with prednisolone and chlorambucil is the treatment approach best supported by our evidence. Ciclosporin should be avoided in this subset. Funding Medical Research Council, Novartis, Renal Association, Kidney Research UK.
Ethical issues in dialysis therapy Jha, Vivekanand, Prof; Martin, Dominique E, PhD; Bargman, Joanne M, MD ...
The Lancet (British edition),
05/2017, Letnik:
389, Številka:
10081
Journal Article
Recenzirano
Odprti dostop
Summary Treatment for end-stage kidney disease is a major economic challenge and a public health concern worldwide. Renal-replacement therapy poses several practical and ethical dilemmas of global ...relevance for patients, clinicians, and policy makers. These include how to: promote patients' best interests; increase access to dialysis while maintaining procedural and distributive justice; minimise the influence of financial incentives and competing interests; ensure quality of care in service delivery and access to non-dialytic supportive care when needed; minimise the financial burden on patients and health-care system; and protect the interests of vulnerable groups during crisis situations. These issues have received comparatively little attention, and there is scant ethical analysis and guidance available to decision makers. In this Health Policy, we provide an overview of the major ethical issues related to dialysis provision worldwide, identify priorities for further investigation and management, and present preliminary recommendations to guide practice and policy.
Background Skeletal muscle wasting in chronic kidney disease (CKD) is associated with morbidity and mortality. Resistance exercise results in muscle hypertrophy in the healthy population, but is ...underinvestigated in CKD. We aimed to determine the feasibility of delivering a supervised progressive resistance exercise program in CKD, with secondary aims to investigate effects on muscle size, strength, and physical functioning. Study Design Parallel randomized controlled feasibility study. Setting & Participants Patients with CKD stages 3b to 4 were randomly assigned to the exercise (n = 20; 11 men; median age, 63 IQR, 57-65 years; median estimated glomerular filtration rate, 28.5 IQR, 19.0-32.0 mL/min/1.73 m2 ) or nonexercise control (n = 18; 14 men; median age, 66 IQR, 45-79 years; estimated glomerular filtration rate, 20.5 IQR, 16.0-26.0 mL/min/1.73 m2 ) group. Intervention Patients in the exercise group undertook an 8-week progressive resistance exercise program consisting of 3 sets of 10 to 12 leg extensions at 70% of estimated 1-repetition maximum thrice weekly. Patients in the control group continued with usual physical activity. Outcomes Primary outcomes were related to study feasibility: eligibility, recruitment, retention, and adherence rates. Secondary outcomes were muscle anatomical cross-sectional area, muscle volume, pennation angle, knee extensor strength, and exercise capacity. Measurements Two- and 3-dimensional ultrasonography of skeletal muscle, dynamometry, and shuttle walk tests at baseline and 8 weeks. Results Of 2,349 patients screened, 403 were identified as eligible and 38 enrolled in the study. 33 (87%) completed the study, and those in the exercise group attended 92% of training sessions. No changes were seen in controls for any parameter. Progressive resistance exercise increased muscle anatomical cross-sectional area, muscle volume, knee extensor strength, and exercise capacity. Limitations No blinded assessors, magnetic resonance imaging not used to assess muscle mass, lack of a healthy control group. Conclusions This type of exercise is well tolerated by patients with CKD and confers important clinical benefits; however, low recruitment rates suggest that a supervised outpatient-based program is not the most practical implementation strategy.
Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of ...awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries.
Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 73% versus intervention 874/1,123 78%; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 59% versus intervention 548/1,123 49%; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 20% versus intervention 21/178 11.8%; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily.
This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.
Chronic kidney disease (CKD) is an important global public health problem that is associated with adverse health outcomes and high health care costs. Effective and cost-effective treatments are ...available for slowing the progression of CKD and preventing its complications, including cardiovascular disease. Although wealthy nations have highly structured schemes in place to support the care of people with kidney failure, less consideration has been given to health systems and policy for the much larger population of people with non–dialysis-dependent CKD. Further, how to integrate such strategies with national and international initiatives for control of other chronic noncommunicable diseases (NCDs) merits attention. We synthesized the various approaches to CKD control across 17 European countries and present our findings according to the key domains suggested by the World Health Organization framework for NCD control. This report identifies opportunities to strengthen CKD-relevant health systems and explores potential mechanisms to capitalize on these opportunities. Across the 17 countries studied, we found a number of common barriers to the care of people with non–dialysis-dependent CKD: limited work force capacity, the nearly complete absence of mechanisms for disease surveillance, lack of a coordinated CKD care strategy, poor integration of CKD care with other NCD control initiatives, and low awareness of the significance of CKD. These common challenges faced by diverse health systems reflect the need for international cooperation to strengthen health systems and policies for CKD care.
Despite guidance and evidence for the beneficial effects of intradialytic exercise (IDE), such programmes are rarely adopted within practice and little is known about how they may best be sustained. ...The Theoretical Domains Framework (TDF) was used to guide the understanding of the barriers and facilitators to initial and ongoing IDE participation and to understand how these are influential at each stage.
Focus groups explored patient (n=24) and staff (n=9) perceptions of IDE prior to the introduction of a programme and, six months later, face to face semi-structured interviews captured exercising patients (n=11) and staffs' (n=8) actual experiences. Data were collected at private and NHS haemodialysis units within the UK. All data were audio-recorded, translated where necessary, transcribed verbatim and subject to framework analysis.
IDE initiation can be facilitated by addressing the pre-existing beliefs about IDE through the influence of peers (for patients) and training (for staff). Participation was sustained through the observation of positive outcomes and through social influences such as teamwork and collaboration. Despite this, environment and resource limitations remained the greatest barrier perceived by both groups.
Novel methods of staff training and patient education should enhance engagement. Programmes that clearly highlight the benefits of IDE should be more successful in the longer term. The barrier of staff workload needs to be addressed through specific guidance that includes recommendations on staffing levels, roles, training and skill mix.
Immunoglobulin A nephropathy (IgAN) is linked inextricably to the name Jean Berger, the Parisian pathologist who published the first description of IgAN in 1968. We reflect on the significance of ...Berger's first report and consider 40 years of progress in our understanding of IgAN since it was published. We also look back to the days before Berger, when IgAN could not have been identified (because there were no techniques for detecting IgA deposits), classification of glomerulonephritis was even more contentious and confusing than it is today, and it is likely that the literature describing focal glomerulonephritis contained many of the cases we would now identify as IgAN.
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