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In this trial in persons with chronic kidney disease and type 2 diabetes, combination therapy with finerenone and empagliflozin led to a greater reduction in the urinary albumin-to-creatinine ratio than either drug alone.

Loss of normal kidney function affects more than 10% of the population and contributes to morbidity and mortality. Kidney diseases are currently treated with immunosuppressive agents, antihypertensives and diuretics with partial but limited success. Most kidney disease is characterized by breakdown of the glomerular filtration barrier (GFB). Specialized podocyte cells maintain the GFB, and structure–function experiments and studies of intercellular communication between the podocytes and other GFB cells, combined with advances from genetics and genomics, have laid the groundwork for a new generation of therapies that directly intervene at the GFB. These include inhibitors of apolipoprotein L1 (APOL1), short transient receptor potential channels (TRPCs), soluble fms-like tyrosine kinase 1 (sFLT1; also known as soluble vascular endothelial growth factor receptor 1), roundabout homologue 2 (ROBO2), endothelin receptor A, soluble urokinase plasminogen activator surface receptor (suPAR) and substrate intermediates for coenzyme Q10 (CoQ10). These molecular targets converge on two key components of GFB biology: mitochondrial function and the actin–myosin contractile machinery. This Review discusses therapies and developments focused on maintaining GFB integrity, and the emerging questions in this evolving field.Numerous kidney diseases are characterized by a breakdown of the glomerular filtration barrier, which forms the interface between the blood and urine. In this Review, Daehn and Duffield discuss strategies to target components of this barrier, focusing on mechanisms to control mitochondrial function and the actin–myosin machinery, to improve kidney function in individuals with kidney diseases.

Objective To define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease.Design Collaborative prospective meta-analysis of randomised trials.Data sources and eligibility Participating randomised trials of drugs to lower blood pressure compared with placebo or each other or that compare different blood pressure targets, with at least 1000 patient years of follow-up per arm.Main outcome measures Major cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually and all cause death.Participants 26 trials (152 290 participants), including 30 295 individuals with reduced estimated glomerular filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73m2.Data extraction Individual participant data were available for 23 trials, with summary data from another three. Meta-analysis according to baseline kidney function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure were estimated with a random effects model.Results Compared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events by about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect (P=1.00 for homogeneity). The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/β blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR (all P>0.60 for homogeneity).Conclusions Blood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR. There is little evidence from these overviews to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.

In this double-blind trial, patients with chronic kidney disease and type 2 diabetes were randomly assigned to receive the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone or placebo. Treatment with finerenone resulted in lower risks of chronic kidney disease outcomes and cardiovascular outcomes than placebo.

In patients with type 2 diabetes and chronic kidney disease, weekly semaglutide significantly reduced risks of major kidney events, cardiovascular events, and death from any cause while slowing loss of kidney function.

Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis. This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus with lupus nephritis according to the American College of Rheumatology criteria, and a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible. Patients were randomly assigned (1:1) to oral voclosporin (23·7 mg twice daily) or placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low-dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks defined as a composite of urine protein creatinine ratio of 0·5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 mL/min/1·73 m2 or no confirmed decrease from baseline in eGFR of >20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or for 7 or more days during weeks 44 through 52, just before the primary endpoint assessment. Safety was also assessed. Efficacy analysis was by intention-to-treat and safety analysis by randomised patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03021499. Between April 13, 2017, and Oct 10, 2019, 179 patients were assigned to the voclosporin group and 178 to the placebo group. The primary endpoint of complete renal response at week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio 2·65; 95% CI 1·64–4·27; p<0·0001). The adverse event profile was balanced between the two groups; serious adverse events occurred in 37 (21%) of 178 in the voclosporin group and 38 (21%) of 178 patients in the placebo group. The most frequent serious adverse event involving infection was pneumonia, occurring in 7 (4%) patients in the voclosporin group and in 8 (4%) patients in the placebo group. A total of six patients died during the study or study follow-up period (one [<1%] patient in the voclosporin group and five [3%] patients in the placebo group). None of the events leading to death were considered by the investigators to be related to the study treatments. Voclosporin in combination with MMF and low-dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low-dose steroids alone, with a comparable safety profile. This finding is an important advancement in the treatment of patients with active lupus nephritis. Aurinia Pharmaceuticals.

In this trial, patients with CKD (with or without type 2 diabetes) were randomly assigned to receive dapagliflozin or placebo. The primary composite outcome — a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes — was less frequent with dapagliflozin.

Among patients with heart failure and a reduced ejection fraction, those who received the SGLT2 inhibitor empagliflozin had a significantly lower incidence of cardiovascular death or hospitalization for heart failure than those who received placebo.