Thrombocytopenia and Kidney disease, two possible hallmark of FCS phenotype: preliminary evidence from a cohort study

Abstract

Background and Aim: Familial Chylomicronemia Syndrome (FCS) is a rare monogenic autosomal recessive disorder of lipid metabolism determining severe hypertriglyceridemia (HTG). As the use of Volanesorsen, a novel FCS treating drug, has been associated with thrombocytopenia, the relationship between FCS and low platelets counts should be firmly established. It has been reported also kidney complication in FCS, but the data are sparse. To this aim, we have retrospectively evaluated the spontaneous variation of platelet counts and Kidney impairment in a cohort of patients with FCS. Methods: Single-center retrospective cohort study on 20 FCS patients included in the LIPIGEN. Medical charts have been revised to collect retrospectively information on kidney function in a cohort of patients with FCS. Results: Across the study population, the median PLT count was 187,225 platelet/mcL. The median on treatment TG levels in the whole cohort was 1309 mg/dl. During follow-up, 8 (44.4%) patients experienced at least one episode of mild and 1 (5%) of moderate thrombocytopenia. None had severe thrombocytopenia. Mean triglycerides do not significantly predict mean platelet values. However, when considering a multivariate model including mean triglycerides, sex, the presence of hepatic steatosis and age we found that male sex and the presence of ultrasound estimated hepatic steatosis were associated with significantly lower platelet (respectively β-0,473, P=0,044 and β-0,469, P=0,048). Age was of borderline statistical significance (β-0,388, P=0,087). Across the study population, the median GFR values was 99.5 ml/min. Median eGFR was significantly associated with history of hypertension (β-0,508, P=0,031). Overall, proteinuria occurred in 5 (25%) patients, and it did not associate with hypertension, diabetes, age, sex nor triglyceride levels. Four (20.0%) patients meet the criteria of hyperfiltration whereas 3 (15.0%) were exhibiting an eGFR below 90 ml/min. Among hyperfiltrating, two had also proteinuria in at least one occasion during life. One patient with eGFR below 90 ml/min and proteinuria had a biopsy-proven diagnosis of glomerulonephritis. Overall, the impairment in kidney function was independent from age, diabetes, hypertension, median TGs, AP, sex. Conclusions: The present analysis confirmed that thrombocytopenia and kidney impairment might be a clinical characteristics of FCS phenotype. Further studies in larger cohort are needed to better clarify if kidney disease and thrombocytopenia might be a hallmark of FCS in broader population and understand the potential patho-physiological mechanism.