D’Erasmo et al. shift the focus away from pancreatitis by systematically characterising renal involvement in familial and multifactorial chylomicronemia syndromes. Renal biopsies taken from patients exhibiting persistent chylomicronemia alongside nephrotic-range proteinuria revealed evidence of lipid-driven glomerular injury. This was characterised by the presence of foam cell infiltration and lipoprotein ‘pseudothrombi’, which are consistent with a phenotype resembling lipoprotein glomerulopathy in the absence of pathogenic APOE variants. In a pooled cohort of 84 adults with genetically defined FCS or MCS, over one-third had a history of proteinuria, almost half had reduced eGFR and more than 40% had hyperfiltration, which far exceeds the rates observed in general population surveys. Hypertension and diabetes emerged as major correlates of proteinuria and eGFR decline, highlighting the importance of systematic renal monitoring and rigorous management of cardiometabolic comorbidities in these rare lipid disorders.

In an accompanying editorial, Moulin presents these observations as a potential ‘new dark side’ of persistent chylomicronemia. He argues that nephropathy should now be considered, alongside acute pancreatitis and ASCVD, as a key complication of FCS and severe MCS. He calls for replication in independent cohorts and for prospective renal surveillance in ongoing trials of anti-apoC-III and anti-ANGPTL3 therapies in patients with hyperchylomicronemia.