This week in Nephrology

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Welcome to This Week in Nephrology. This week we're covering 10 notable papers spanning dialysis decisions and cardiovascular risk in kidney disease, new and old therapies for glomerular disease, and the genetics and safety questions that shape everyday kidney care.

The week's largest trials ask what actually improves outcomes for older and higher-risk patients with kidney disease. In The Lancet, Caskey and colleagues report Prepare for Kidney Care, a pragmatic randomised trial across 31 kidney centres in the United Kingdom [1]. It enrolled 445 people with an eGFR below 15 who were either aged 80 or older, or aged 65 to 79 with frailty or multimorbidity, and the median age was 82. Participants were assigned to prepare for a protocolised form of conservative kidney management, focused on slowing progression, symptom control and quality of life, or to prepare for dialysis. After a mean follow-up of four and a half years, quality-adjusted life-years were slightly lower with conservative management, but the difference was not statistically significant. Dialysis access complications were about sixty percent lower in the conservative arm, though based on only 74 events, and hospital admission rates were similar. Deaths occurred in 69 percent of the conservative group and 63 percent of the dialysis group. The trial did not show that preparing for dialysis delivers more quality-adjusted life in this population, and it gives randomised evidence, previously absent, to inform shared decisions in frail older patients. In the New England Journal of Medicine, Ridker and colleagues report the ZEUS trial of ziltivekimab, an interleukin-6 antibody, in 6376 adults with atherosclerotic disease, chronic kidney disease and a raised C-reactive protein [2]. The drug lowered free interleukin-6 by about three quarters relative to placebo, yet major cardiovascular events occurred in just under 18 percent of patients in both arms over almost three years. Serious infections were slightly more frequent with the drug. This is a clearly negative trial for the inflammation hypothesis in this kidney population. Also in the New England Journal of Medicine, Sampaio Silva and colleagues report OPTIMAL-STROKE, conducted at 30 sites in Brazil in 4368 people with previous ischaemic stroke or transient ischaemic attack [3]. Targeting a systolic pressure below 120 rather than below 140 cut major cardiovascular events by about a fifth. The composite kidney outcome of a halving of eGFR or end-stage disease was more common with intensive treatment, so the cardiovascular gain came with a kidney signal that nephrologists will weigh in patients with stroke and reduced kidney function.

In glomerular disease, two IgA nephropathy studies point in different directions, and a lupus cohort examines early treatment targets. In the American Journal of Kidney Diseases, Ouyang and colleagues report the RITA trial, which randomised 106 Chinese adults with persistent proteinuria above one gram a day despite optimised renin-angiotensin blockade to rituximab plus that therapy or the blockade alone [4]. Proteinuria change at twelve months was similar between groups, and there were no significant differences in eGFR, galactose-deficient IgA1 levels, or the share of patients halving their proteinuria. The follow-up was short and only Asian patients were enrolled, but the trial does not support adding B-cell depletion with rituximab to standard care. In Kidney International Reports, Cheung and colleagues present a prespecified interim analysis of SPARTAN, in which 12 newly diagnosed adults with IgA nephropathy who had not received renin-angiotensin blockade were started on sparsentan as first-line treatment [5]. Proteinuria fell by roughly seventy percent over 24 weeks, and 58 percent of patients reached complete remission. Urinary markers of inflammation and fibrosis also fell. Dizziness affected half of the patients, and one patient stopped because of hypotension. With twelve patients and no control group, this is hypothesis-generating evidence for first-line use, well short of what would change practice. Also in Kidney International Reports, Umeda and colleagues studied the European Alliance of Associations for Rheumatology early targets in a retrospective cohort of around 290 adults with proliferative lupus nephritis [6]. Patients who met the three-month and six-month targets had roughly sixty percent lower odds of a thirty percent eGFR decline at two years, with the event rate about half that of non-achievers. In a landmark analysis, the proteinuria-reduction component carried the prognostic information beyond early kidney function. This is observational support for using early proteinuria response as a prognostic marker.

Genetic kidney disease features in two papers that bear on diagnosis and counselling. In Kidney International, Robert and colleagues re-examined a widely cited estimate that one in 106 people carry a pathogenic COL4A3 or COL4A4 variant [7]. Using a much larger population database, a clinical exome cohort of over 29,000 patients and a stricter expert curation strategy, they estimate autosomal dominant Alport syndrome at about one in 283 people, and showed that in silico tools misclassified common glycine substitutions. That figure is far above classical clinical estimates but well below the earlier one. Qualifying variants appeared in one in 44 patients with kidney disease, which the authors argue justifies systematic screening in chronic kidney disease. In the Clinical Journal of the American Society of Nephrology, Lobo and colleagues review reproductive health in polycystic kidney disease, Alport spectrum disorders, Fabry disease and monogenic podocytopathies [8]. They note that adverse pregnancy outcomes are driven mainly by kidney function, hypertension, proteinuria and prior preeclampsia, with genotype shaping counselling. The review covers transition of fetotoxic drugs such as tolvaptan, SGLT2 inhibitors and mycophenolate, and options including preimplantation genetic testing, while stating that the evidence base is largely retrospective and enriched for milder disease.

Two Japanese studies address procedural and toxic kidney harms. In Kidney International Reports, Suzukawa and colleagues used a national inpatient database of 78,817 native kidney biopsies to build a pre-biopsy bleeding score [9]. Major bleeding requiring transfusion or intervention occurred in about one and a half percent of biopsies. Acute kidney injury carried roughly elevenfold higher odds of bleeding than chronic glomerulonephritis, and older age and lower body mass index added risk. Just over half of patients scored two or less, and their bleeding risk was under half a percent. The score has only internal validation, but it offers a framework for outpatient biopsy pathways. Also in Kidney International Reports, Doi and colleagues followed 190 adults with kidney injury linked to specific red yeast rice supplements during the 2023 to 2024 outbreak, which often presented as acquired Fanconi syndrome [10]. The tubular abnormalities resolved within about four months in at least four in five patients, but eGFR improved only over the first two months and then plateaued. Among patients presenting with an eGFR below 60, only a third had recovered above that level by eighteen months. Six patients needed acute dialysis and one remained on permanent kidney replacement. The authors conclude that biochemical recovery does not signal recovery of filtration function.

If you only have time for one paper this week, make it Prepare for Kidney Care in The Lancet [1]. It is the first randomised evidence comparing conservative kidney management with dialysis preparation in frail and older patients, and it reopens a question many units had answered by habit.

That's your roundup for This Week in Nephrology. The full transcript and references are available on the episode page. See you next week.

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