The hidden burden of kidney damage in chylomicronemia syndromes

It has been recognized that hypertriglyceridemia (HTG) is associated with kidney damage. Monogenic and polygenic causes of extreme HTG characterized by severe chylomicronemia (TG > 885 mg/dl or 10 mmol/L) constitute unique models to investigate the potential nephrotoxic effects of sustained and severe exposure to HTG.

This study had two components: (1) kidney biopsies of three patients with severe chylomicronemia and proteinuria were analyzed; (2) a cross-sectional review of the medical files of two independent cohorts of patients with the Familial Chylomicronemia Syndrome (FCS) or Multifactorial Chylomicronemia Syndrome (MCS) followed in Italy and Canada was performed. Renal involvement was defined by the presence of proteinuria, reduced eGFR (<90 mL/min/1.73 m²), or hyperfiltration (≥105 mL/min/1.73 m²).

Histological findings in the three patients with severe chylomicronemia revealed diverse patterns of glomerular injury, including lipid-laden glomerular damage, foam-cell infiltration, all consistent with lipid-associated nephropathy. Among the 84 adults with severe chylomicronemia (38 F CS, 46 MCS), 35 % had a history of proteinuria, 49 % presented eGFR<90 mL/min/1.73 m², 8 % had eGFR<60 mL/min/1.73 m², and 41 % showed hyperfiltration. Hypertension and diabetes emerged as independent covariates for proteinuria and reduced eGFR.

These data suggest that severe chylomicronemia due to FCS and MCS is predominantly associated with proteinuria, which might be the possible consequences of lipid-laden glomerular injury. Therefore, renal disease should be included in the list of possible complications of severe chylomicronemia, thus suggesting that renal monitoring have to be considered as part of clinical management of these conditions.