Damage to the endothelial glycocalyx, which helps maintain vascular homeostasis, heightens the sensitivity of the vasculature to atherogenic stimuli. Patients with renal failure have endothelial dysfunction and increased risk for cardiovascular morbidity and mortality, but the state of the endothelial glycocalyx in these patients is unknown. Here, we used Sidestream Darkfield imaging to detect changes in glycocalyx dimension in dialysis patients and healthy controls from in vivo recordings of the sublingual microcirculation. Dialysis patients had increased perfused boundary region and perfused diameters, consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties. These patients also had higher serum levels of the glycocalyx constituents hyaluronan and syndecan-1 and increased hyaluronidase activity, suggesting the shedding of these components. Loss of residual renal function had no influence on the imaging parameters but did associate with greater shedding of hyaluronan in blood. Furthermore, patients with higher levels of inflammation had more significant damage to the glycocalyx barrier. In conclusion, these data suggest that dialysis patients have an impaired glycocalyx barrier and shed its constituents into blood, likely contributing to the sustained endothelial cell activation observed in ESRD.
1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles. 2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (SD 22) in the daytime, a minimum of 86 ml/min (SD 12) at night and with a relative amplitude of 33% (SD 15). 3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well. 4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion. 5. Urinary albumin and beta 2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm. 6. The highest quantity of sodium, water and beta 2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.
Abstract. Andreev E, Koopman M, Arisz L (Medical University-Sofia, Sofia, Bulgaria and University of Amsterdam, Amsterdam, The Netherlands). A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible? (Review.) J Intern Med 1999; 246: 247±252. This is a review of the available information about drugs which cause an increase in plasma creatinine concentration without decreasing glomerular filtration rate (GFR). The GFR is the main, but not the single, determinant of the plasma creatinine levels. Several drugs, such as cimetidine, trimethoprim, corticosteroids, pyrimethamine, phenacemide, salicylates and active vitamin D metabolites, have been reported to increase plasma creatinine without influencing its glomerular filtration. Cimetidine, trimethoprim, pyrimethamine and salicylates can inhibit secretion of creatinine by the proximal tubule. Corticosteroids and vitamin D metabolites probably modify the production rate and the release of creatinine. The exact mechanism of phenacemide±creatinine interaction is not fully explained. These drug-induced alterations in plasma creatinine concentration have clinical significance when GFR is estimated by using plasma creatinine.
The arterial wall of FH patients is characterized by increased inflammation, which is markedly reduced after lipoprotein apheresis. This lends support to a causal role of apoprotein B-containing lipoproteins in arterial wall inflammation and supports the concept that lipoprotein-lowering therapies may impart anti-inflammatory effects by reducing atherogenic lipoproteins.
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