Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

A search for the lowest mass scalar glueball in Double Pomeron Exchange

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The effectiveness and value of belimumab and voclosporin for lupus nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects between 300,000 and 1.5 million Americans.1 It is more common in women (90% of diagnosed cases) and in non-Whites (4 times higher prevalence in Black patients; 2 times higher prevalence in Hispanic patients). Approximately half of patients with SLE will be diagnosed with lupus nephritis (LN), characterized by inflammation in the kidney, proteinuria, and progressive kidney damage that can lead to kidney failure.2,3 LN typically presents in patients who are aged 20-40 years,4,5 and it is the most common cause of death and disability in patients with SLE. Guidelines for the treatment of LN recommend induction therapy with high-dose corticosteroids combined with either mycophenolate mofetil (MMF) or cyclophosphamide, followed by maintenance therapy with MMF.6,7 Unfortunately, fewer than half of patients with LN respond to current combination therapy, so there is a large unmet need for new therapies. The US Food and Drug Administration (FDA) recently approved 2 new therapies for LN. Belimumab, a parenteral B-lymphocyte inhibitor already approved by the FDA for SLE, was approved for LN in December 2020. Voclosporin, an oral calcineurin inhibitor that is reported to be safer than other calcineurin inhibitors (less kidney damage), was approved in January 2021. The Institute for Clinical and Economic Review (ICER) conducted a systematic literature review and cost-effectiveness analysis to evaluate the health and economic outcomes of belimumab and voclosporin to treat LN. Complete details of ICER’s systematic literature search and protocol, as well as the methodology and model structure for the economic evaluation, are available on ICER’s website. Here, we present the summary of our findings and highlights of the policy discussion with key stakeholders held at a public meeting of the New England Comparative Effectiveness Public Advisory Council on March 26, 2021. The detailed report is available on the ICER website at https://icer.org/wp-content/uploads/2020/11/ICER_Lupus-Nephritis_Final-Evidence-Report_041621.pdf

The cost-effectiveness of belimumab and voclosporin for patients with Lupus Nephritis in the United States

Background and objectives: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. Design, setting, participants, & measurements: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: “complete response,” “partial response,” and “active disease” defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active–Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan–Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored. Results: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately$150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69$66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year. Conclusions: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of$100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin