Nephrology

RAAS inhibitors outperform CCBs for kidney outcomes and BP in pediatric CKD hypertension

This target-trial emulation compared incident RAAS inhibitor versus calcium channel blocker therapy in 2–20-year-olds with CKD stages 2–4 and hypertension. Propensity weighting balanced demographics, CKD etiology, proteinuria, CKD stage, BP control, and comorbidities between 1,757 RAASi and 1,005 CCB initiators. RAAS inhibition was associated with a lower adjusted risk of kidney replacement therapy and adverse eGFR composite outcomes over two years than CCBs. RAASi therapy also produced better systolic BP control than CCBs in the first two years of treatment. 1

hsCRP ≥2 mg/L signals excess cardiovascular events and death in CKD, and ESKD risk in diabetics

This propensity-matched cohort used TRINETX data to compare 27,580 CKD patients with hsCRP ≥2 mg/L versus 27,580 with hsCRP <2 mg/L. Groups were well matched for traditional cardiovascular risks, baseline therapies, eGFR, and albuminuria. hsCRP ≥2 mg/L was associated with markedly higher risks of MACE and death, independent of traditional risk factors. High hsCRP did not increase ESKD risk overall but coincided with higher ESKD risk among diabetic patients. 2

UNDERSCORE tool predicts successful RRT weaning in severe ICU AKI using six routine variables

This post-hoc AKIKI/AKIKI2 analysis included 180 ICU patients with KDIGO stage 3 AKI who underwent an RRT weaning attempt of at least three days. Fifty-six percent were successfully weaned, defined as no RRT resumption within seven days after discontinuation. Six predictors formed the UNDERSCORE tool: RRT duration before attempt, septic shock on admission, baseline creatinine, vasopressor use, mechanical ventilation, and urine output after the attempt. Discrimination was strong in the derivation cohort (AUC 0.86) and fair in an independent Swiss ICU validation cohort (AUC 0.73). 3

Anti-PLA2R1 IgG drives ADAM10/17-mediated PLA2R1 shedding and GBM-anchored deposits in membranous nephropathy

This mechanistic study used PLA2R1-expressing podocytes, engineered HEK293 cells, and kidney biopsies to clarify subepithelial deposit formation in PLA2R1-associated membranous nephropathy. PLA2R1-positive MN sera or purified anti-PLA2R1 IgG increased PLA2R1 C-terminal fragments and soluble ectodomain, which were blocked by ADAM10/17 inhibitors and ectodomain decoys. Shedding was epitope- and antibody-dependent, complement-independent, and absent with antibody-binding–deficient PLA2R1 or unrelated THSD7A antigen. Biopsies showed PLA2R1 ectodomain enriched in GBM deposits, whereas intracellular domains remained podocyte-restricted, confirmed by dual-label immunogold microscopy. 4