How certain are El Niño–Southern Oscillation frequency changes in Coupled Model Intercomparison Project Phase 6 models?

El Niño–Southern Oscillation (ENSO) is one of the most important modes of climate variability on interannual timescales. We aim to find out whether a change in ENSO frequency can be predicted for the nearer future. We analyse the unforced pre‐industrial control run and the forced 1%/year CO2 increase run for an ensemble of 43 general circulation models that participated in the Coupled Model Intercomparison Project Phase 6 (CMIP6). We assume that the uncertainty of ENSO frequency trend estimates from an ensemble is caused by apparent trends as well as model differences. The part of the uncertainty caused by apparent trends is estimated from the pre‐industrial control simulations. As a measure for ENSO frequency, we use the number of El Niño‐ and La Niña‐like months in a moving 30‐year time window. Its linear decadal trend is calculated for every member. The multimember mean of the trend for both experiments is less than 0.7 events per decade. Given that the standard error is of the same order of magnitude, we consider this a negligible trend. The uncertainties are large in both experiments and we can attribute most of the intermember variability to apparent trends due to natural variability rather than different model reactions to CO2 forcing. This means that the impact of intermodel differences might have been overstated in previous studies. Apparent trends make it very difficult to make reliable predictions of changes in ENSO frequency based on 120‐year time series.The 1pctCO2 and piControl ensembles from CMIP6 are analysed for 43 models with a focus on changes in ENSO frequency. We find that most of the intermember variability can be attributed to natural variability instead of model differences. Therefore, the uncertainty can only marginally be reduced and it is very difficult to reliably predict changes in ENSO frequency on a timescale of 150 years.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659https://doi.org/10.5281/zenodo.684196

Effects of allopurinol on the progression of chronic kidney disease

Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known.In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation.Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group.In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.)