Complement inhibitors arrive without a rulebook, and KDIGO asks why the guidelines are not being followed

The edition in brief

The 2025 International Society of Nephrology Forum on Complement Therapeutics addressed the awkward position the field is in: alternative pathway complement inhibitors have succeeded in trials in C3 glomerulopathy, immune-complex membranoproliferative glomerulonephritis and IgA nephropathy, and nobody yet knows how to select patients for them. Complement overactivation drives C3G and IC-MPGN; in IgA nephropathy it is a secondary contributor to a multifactorial disease. The panel identified complement biomarkers, complement autoantibodies, genetics and the kidney biopsy as the four candidate selection tools, and marked all four as unresolved. A systematic review of 23 studies assessed fibroblast growth factor 23 in acute kidney injury: pooled sensitivity 0.79 (95% CI 0.73 to 0.86), specificity 0.82 (0.75 to 0.89), summary ROC area 0.87 (0.81 to 0.92) for diagnosis, with intact FGF23 outperforming the C-terminal assay (0.91 vs 0.81), and weaker performance for mortality (area 0.77). Heterogeneity was substantial throughout. The FDA approved a supplement to Boehringer Ingelheim's empagliflozin-metformin extended-release application, SYNJARDY XR, on 11 August; the record names the application, not what changed. Near-infrared autofluorescence tracked tubular epithelial injury across three mouse models without any injected probe, with coproporphyrin III identified as the likely fluorophore, and correlated inversely with eGFR in 34 human nephrectomy samples - proof of concept, not a clinical test. A KDIGO implementation summit in Kuala Lumpur, with participants from 13 Asia-Pacific countries, set out why the diabetes and blood pressure guidelines in chronic kidney disease are not reaching patients, and proposed solutions graded by country income level.