This week in Nephrology

Welcome to This Week in Nephrology. This week we're covering 10 notable papers spanning new guidance and drug strategies in glomerular and anaemia care, the cardio-kidney-metabolic axis with risk prediction, and transplantation plus the biology of repair and cyst growth. Let's dive in.

We start with the week's most immediately practice-relevant document. Annals of Internal Medicine carries a synopsis by Hedayati and colleagues of the Kidney Disease Improving Global Outcomes 2026 guideline on anaemia in chronic kidney disease, the first full update since 2012 [1]. Eight graded recommendations sit alongside 49 practice points, and several will change clinic behaviour. Transferrin saturation and ferritin thresholds are used to guide iron therapy, with intravenous iron preferred over oral iron in people on haemodialysis. Correctable causes of anaemia should be addressed before reaching for either an erythropoiesis-stimulating agent or a hypoxia-inducible factor prolyl hydroxylase inhibitor, and when pharmacotherapy is needed, the work group recommends an erythropoiesis-stimulating agent rather than a hypoxia-inducible factor inhibitor as first-line treatment. That is a notable position given the enthusiasm around the oral agents. Haemoglobin thresholds for starting an agent are explicitly individualised to symptoms, characteristics and patient values rather than fixed, but the upper haemoglobin target during maintenance therapy stays conservative, below 11.5 grams per decilitre. The large number of ungraded practice points is itself the message — much of anaemia management remains expert consensus rather than trial-driven.

Turning to glomerular disease, Nephrology Dialysis Transplantation reports combination therapy with sparsentan and sodium-glucose cotransporter-2 inhibitors in IgA nephropathy, from Ayoub and colleagues [3]. Two open-label datasets are presented. In the SPARTACUS trial, 48 patients already on a stable sodium-glucose cotransporter-2 inhibitor had their renin-angiotensin system inhibitor swapped for sparsentan; albuminuria fell rapidly and stayed down through 24 weeks, with a reduction of roughly 56 percent. The mirror-image question was asked in a substudy of the PROTECT open-label extension, where 63 patients on sparsentan were randomised to add a sodium-glucose cotransporter-2 inhibitor or continue sparsentan alone for 12 weeks. Here the added benefit was more modest but statistically significant, with proteinuria about a quarter lower in the combination arm relative to sparsentan alone. Tolerability was reassuring, with few severe or treatment-limiting adverse events and no unexpected safety signals. The practical read is that these are short, open-label, proteinuria-endpoint studies rather than outcome trials, but they support the sequencing question clinicians actually face — you can move a patient from a renin-angiotensin blocker to sparsentan on top of an established sodium-glucose cotransporter-2 inhibitor, and you can layer the inhibitor onto sparsentan, in both directions safely. Complementing that, the American Journal of Kidney Diseases offers a core curriculum review from Thurman and Poppelaars on complement in kidney disease [2], a useful orientation now that complement inhibitors are approved across five renal indications — atypical haemolytic uraemic syndrome, C3 glomerulopathy, immune-complex membranoproliferative glomerulonephritis, antineutrophil cytoplasmic antibody-associated vasculitis, and IgA nephropathy. Their point is that conventional immunosuppression does not directly block complement, and that complement diagnostics in plasma, urine and tissue are now part of the routine work-up rather than a research curiosity.

The cardio-kidney-metabolic theme is well represented, with two reviews both in the Clinical Journal of the American Society of Nephrology. Correa and colleagues tackle atherosclerotic cardiovascular disease in chronic kidney disease, making the sobering observation that most patients with chronic kidney disease die of cardiovascular causes before ever reaching kidney failure [4]. Risk rises steeply as filtration falls and albuminuria rises, reaching several-fold elevations in myocardial infarction, stroke and peripheral arterial disease at the extremes. Their central argument is that this burden is under-recognised and undertreated, partly because presentations are atypical, partly because conventional risk calculators underestimate risk in this group, and partly because patients with advanced chronic kidney disease were excluded from most landmark cardiovascular trials. They review chronic-kidney-disease-adapted risk equations, cardiac biomarkers and non-invasive imaging, along with lipid lowering, antiplatelet and blood pressure therapy, revascularisation, and the newer cardiometabolic agents. Mathew and colleagues take the adiposity side of the same problem [5], tracing obesity-related kidney injury through glomerular hyperfiltration and raised intraglomerular pressure as well as indirect pathways via diabetes and hypertension, and noting that visceral and perirenal fat depots specifically track with chronic kidney disease. Their management framework has shifted decisively from lifestyle alone to multimodal care built around incretin-based therapy, with sodium-glucose cotransporter-2 inhibitors contributing modest weight loss alongside cardio-kidney protection and bariatric surgery associated with improved cardio-kidney outcomes. They are candid that data on triple incretin agonists in kidney disease remain limited.

Risk identification is where Kidney International Reports adds something concrete. Kosugi and colleagues developed and externally validated a model predicting progression to high-risk chronic kidney disease by the Kidney Disease Improving Global Outcomes classification at five years, using a nationwide Japanese health checkup cohort [9]. The development set included roughly 295,000 participants and the external validation set nearly 120,000, with discrimination good and essentially identical across both, around 0.82. Predictors are all primary-care-available — age, sex, body mass index, systolic blood pressure, haemoglobin A1c, triglycerides, uric acid, estimated filtration rate, proteinuria, antihypertensive and antidiabetic medication, smoking and prior stroke — and the authors provide a nomogram. Decision curve analysis supported net clinical benefit. The obvious caveat is that this is a Japanese screening population, so calibration elsewhere is unproven, but it fills a real gap: most validated equations predict failure in established chronic kidney disease rather than identifying who will get there.

On to transplantation, where the American Journal of Transplantation documents a genuine structural shift in the donor pool. Husain and colleagues analysed national registry data and found that donation after circulatory death rose from about a fifth of kidney donors in 2016 to 2019, to roughly three in ten, and then to over 40 percent in the most recent era — and by the second quarter of 2025, just over half of all kidney donors were donation after circulatory death [7]. But the nonuse rate for recovered donation-after-circulatory-death kidneys also climbed, from about a fifth to more than a third, and recently transplanted donation-after-circulatory-death kidneys increasingly come from donors over 60 with diabetes, hypertension and obesity, with nearly 87 percent machine perfused. Variation between organ procurement organisations and between transplant centres remains enormous, from essentially zero to around 60 percent. The message for anyone counselling waitlisted patients is that donation after circulatory death is no longer a marginal category, and that centre-level practice, not organ biology alone, determines what gets used. Also in the Clinical Journal of the American Society of Nephrology, Jonker and colleagues re-analysed the ALLEGRO trial to ask whether plasma tacrolimus concentration outperforms the whole blood level we all monitor [8]. Among 295 recipients, higher plasma concentrations in the first month were associated with lower filtration rate at four weeks and higher late plasma levels with lower filtration at two years, while whole blood levels showed no such association, and those differences were statistically significant. Higher late plasma concentration was also associated with roughly doubled odds of moderate-to-severe arteriolar hyalinosis on protocol biopsy, though that rested on only 10 events. Neither measure predicted rejection or infection. This is hypothesis-generating rather than actionable — plasma tacrolimus assays are not routine, and the authors themselves call for larger studies — but it is a plausible explanation for why whole blood troughs correlate so poorly with nephrotoxicity.

Two papers address mechanism. Nature Reviews Nephrology reviews regeneration versus maladaptive repair after acute kidney injury, from Seibt and colleagues, positioning tubular epithelial cells as the sentinels that determine trajectory [6]. Successful repair means surviving tubular cells proliferating and restoring integrity; failed repair means persistent cell-cycle arrest, senescence and secretion of pro-inflammatory and pro-fibrotic mediators that recruit immune cells and ultimately drive fibroblast activation and matrix deposition — the shared final pathway from acute injury to chronic kidney disease. And in the Journal of the American Society of Nephrology, Cao and colleagues report that the cyclin-dependent kinase 4/6 inhibitor abemaciclib, at doses well below oncology dosing, arrested cyst growth in a Pkd1 mouse model of autosomal dominant polycystic kidney disease more effectively than tolvaptan, with late intervention halting progression in females and reversing it in males, mechanistically by restoring axonemal polyglutamylation and ciliary polycystin levels [10]. This is preclinical, and cyclin-dependent kinase inhibitors carry real toxicity in humans, but it is the most interesting repurposing signal in polycystic kidney disease in some time.

If you only have time for one paper this week, make it the Annals of Internal Medicine synopsis of the 2026 anaemia guideline [1]. It is the only item here that changes what you write on a prescription tomorrow, and the recommendation to prefer an erythropoiesis-stimulating agent over a hypoxia-inducible factor inhibitor as first-line therapy will surprise some practices.

Here are the key takeaways from this week in Nephrology. First, in chronic kidney disease anaemia, exclude correctable causes first, prefer intravenous iron in haemodialysis, start with an erythropoiesis-stimulating agent rather than an oral hypoxia-inducible factor inhibitor, individualise the starting haemoglobin, and keep maintenance haemoglobin below 11.5. Second, in IgA nephropathy, sparsentan and sodium-glucose cotransporter-2 inhibitors can be combined in either sequence with good short-term tolerability and additive proteinuria reduction, though the added benefit of layering the inhibitor onto sparsentan is modest. Third, cardiovascular risk in chronic kidney disease is systematically underestimated by standard calculators, and most of these patients die of cardiovascular disease before reaching dialysis — treat accordingly. Fourth, over half of United States kidney donors are now donation after circulatory death, yet more than a third of recovered such kidneys go unused, with striking centre-level variation. And fifth, plasma rather than whole blood tacrolimus may better track nephrotoxicity, but this remains a research tool for now.

That's your roundup for This Week in Nephrology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.