Recognition is increasing for the effect of AKI on patients, and the resulting societal burden from its long-term effects, including development of chronic kidney disease and end-stage renal disease ...needing dialysis or transplantation.2 Few systematic efforts to manage (prevent, diagnose, and treat) AKI have been put in place and few resources have been allocated to inform health-care professionals and the public of the importance of AKI as a preventable and treatable disease.
Summary Background Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional ...differences in acute kidney injury recognition, management, and outcomes. Methods In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. Findings Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 40% patients) and dehydration (1536 38% patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 46% of 1153 vs 518 32% of 1605 in UMICs vs 492 39% of 1260 in HICs) and hypotension in HICs (564 45% of 1260 vs 611 38%% of 1605 in UMICs vs 440 38% of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 12% of 1076) than in HICs (125 10% of 1230) and UMICs (169 11% of 1549). Interpretation We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs. Funding International Society of Nephrology.
Summary Background IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in ...20–40% of patients within 10–20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy. Methods We did a randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries. We recruited patients aged at least 18 years with biopsy-confirmed primary IgA nephropathy and persistent proteinuria despite optimised renin-angiotensin system (RAS) blockade. We randomly allocated patients with a computer algorithm, with a fixed block size of three, in a 1:1:1 ratio to 16 mg/day TRF-budesonide, 8 mg/day TRF-budesonide, or placebo, stratified by baseline urine protein creatinine ratio (UPCR). Patients self-administered masked capsules, once daily, 1 h before breakfast during the treatment phase. All patients continued optimised RAS blockade treatment throughout the trial. Our primary outcome was mean change from baseline in UPCR for the 9-month treatment phase, which was assessed in the full analysis set, defined as all randomised patients who took at least one dose of trial medication and had at least one post-dose efficacy measurement. Safety was assessed in all patients who received the intervention. This trial is registered with ClinicalTrials.gov , number NCT01738035. Findings Between Dec 11, 2012, and June 25, 2015, 150 randomised patients were treated (safety set) and 149 patients were eligible for the full analysis set. Overall, at 9 months TRF-budesonide (16 mg/day plus 8 mg/day) was associated with a 24·4% (SEM 7·7%) decrease from baseline in mean UPCR (change in UPCR vs placebo 0·74; 95% CI 0·59–0·94; p=0·0066). At 9 months, mean UPCR had decreased by 27·3% in 48 patients who received 16 mg/day (0·71; 0·53–0·94; p=0·0092) and 21·5% in the 51 patients who received 8 mg/day (0·76; 0·58–1·01; p=0·0290); 50 patients who received placebo had an increase in mean UPCR of 2·7%. The effect was sustained throughout followup. Incidence of adverse events was similar in all groups (43 88% of 49 in the TRF-budesonide 16 mg/day group, 48 94% of 51 in the TRF-budesonide 8 mg/day, and 42 84% of 50 controls). Two of 13 serious adverse events were possibly associated with TRF-budesonide—deep vein thrombosis (16 mg/day) and unexplained deterioration in renal function in follow-up (patients were tapered from 16 mg/day to 8 mg/day over 2 weeks and follow-up was assessed 4 weeks later). Interpretation TRF-budesonide 16 mg/day, added to optimised RAS blockade, reduced proteinuria in patients with IgA nephropathy. This effect is indicative of a reduced risk of future progression to end-stage renal disease. TRF-budesonide could become the first specific treatment for IgA nephropathy targeting intestinal mucosal immunity upstream of disease manifestation. Funding Pharmalink AB.
In The Lancet, Turgay Saritas and colleagues report a case with the valuable reminder that chronic low-grade infection of an implanted device can lead to glomerulonephritis. This complication was ...first described 50 years ago in patients with implanted cerebral shunts, so-called shunt nephritis, 2 but in this case was associated with a newer and increasingly widely used implanted device, the left ventricular assist device (LVAD).
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.
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.
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