Kidney and vascular function in adult patients with hereditary fructose intolerance

Mol Genet Metab Rep. 2020 May 11:23:100600. doi: 10.1016/j.ymgmr.2020.100600. eCollection 2020 Jun.


Objective: Previous studies have shown that patients with hereditary fructose intolerance (HFI) are characterized by a greater intrahepatic triglyceride content, despite a fructose-restricted diet. The present study aimed to examine the long-term consequences of HFI on other aldolase-B-expressing organs, i.e. the kidney and vascular endothelium. Methods: Fifteen adult HFI patients were compared to healthy control individuals matched for age, sex and body mass index. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) and endothelial function by peripheral arterial tonometry, skin laser doppler flowmetry and the endothelial function biomarkers soluble E-selectin [sE-selectin] and von Willebrand factor. Serum creatinine and cystatin C were measured to estimate the glomerular filtration rate (eGFR). Urinary glucose and amino acid excretion and the ratio of tubular maximum reabsorption of phosphate to GFR (TmP/GFR) were determined as measures of proximal tubular function. Results: Median systolic blood pressure was significantly higher in HFI patients (127 versus 122 mmHg, p = .045). Pulse pressure and cf-PWV did not differ between the groups (p = .37 and p = .49, respectively). Of all endothelial function markers, only sE-selectin was significantly higher in HFI patients (p = .004). eGFR was significantly higher in HFI patients than healthy controls (119 versus 104 ml/min/1.73m2, p = .001, respectively). All measurements of proximal tubular function did not differ significantly between the groups. Conclusions: Adult HFI patients treated with a fructose-restricted diet are characterized by a higher sE-selectin level and slightly higher systolic blood pressure, which in time could contribute to a greater cardiovascular risk. The exact cause and, hence, clinical consequences of the higher eGFR in HFI patients, deserves further study.

Keywords: 95% confidence interval, (95% CI); Blood; CKD-EPI equation based on creatinine and cystatin c combined, (eGFRcr-cys); CKD-EPI equation based on cystatin c, (eGFRcys); CKD-EPI equation based on serum creatinine, (eGFRcr); Case-control study; Fanconi syndrome; Hereditary fructose intolerance; Kidney; Vessels; alanine, (Ala); aldolase B, (ALDOB); arginine, (Arg); asparagine, (Asn); carotid-femoral pulse wave velocity, (cf-PWV); chronic kidney disease epidemiology collaboration, (CKD-EPI); citrulline, (Cit); cysteine, (Cys); difference, (Δ); estimated glomerular filtration rate, (eGFR); glucokinase regulatory protein, (GKRP); glutamic acid, (Glu); glutamine, (Gln); glycine, (Gly); hereditary fructose intolerance, (HFI); histidine, (His); intrahepatic triglyceride, (IHTG); isoleucine, (Ile); laser doppler flowmetry, (LDF); leucine, (Leu); lysine, (Lys); methionine, (Met); ornithine, (Orn); perfusion units, (PU); phenylalanine, (Phe); proline, (Pro); ratio of tubular maximum reabsorption of phosphate to GFR, (TmP/GFR); reactive hyperemia index, (RHI); reactive hyperemia peripheral arterial tonometry, (RH-PAT); serine, (Ser); soluble E-selectin, (sE-selectin); statistical package of social sciences, (SPSS); taurine, (Tau); threonine, (Thr); tryptophan, (Try); tubular reabsorption of phosphate, (TRP); tyrosine, (Tyr); valine, (Val); von willebrand factor, (vWF).