Abstract
BackgroundCertain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT).MethodsCross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia. CD80 mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes.ResultsControls and Fabry patients did not differ in age, eGFR and gender. However, UPCR, uCD80 and podocyturia were significantly higher in Fabry patients than in controls. As expected, Fabry patients not on ERT were younger and a higher percentage were females. Non-ERT Fabry patients had less advanced kidney disease than ERT Fabry patients: UPCR was lower and eGFR higher, but uCD80 and podocyturia did not differ between non-ERT or ERT Fabry patients. There was a significant correlation between uCD80 and UPCR in the whole population (r 0.44, p 0.0005) and in Fabry patients (r 0.42, p 0.0046). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uCD80 expression in cultured podocytes.ConclusionsFabry disease is characterized by early occurrence of increased uCD80 excretion that appears to be a consequence of glycolipid accumulation. The potential for uCD80 excretion to reflect early, subclinical renal Fabry involvement should be further studied.
Highlights
Certain glomerulopathies are associated with increased levels of CD80 (B7-1)
urinary protein/creatinine ratio (UPCR), uCD80/creatinine ratio (uCD80) and podocyturia were significantly higher in Fabry patients (Table 1)
There were no differences in uCD80 excretion or podocyturia between Fabry patients on enzyme replacement therapy (ERT) and not on ERT (Table 2)
Summary
Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT). Fabry nephropathy is a progressive proteinuric nephropathy of metabolic origin with a natural history that expands decades. In this regard, some glycolipids accumulated in Fabry disease, such as lyso-Gb3, are bioactive. Lyso-Gb3 may activate inflammation pathways in renal cells [12]. At concentrations found in the circulation of Fabry patients, lyso-G3 promotes autocrine TGF-β1 and Notch-1 signaling in podocytes, a response that mimics podocyte responses to high glucose concentrations [14, 17]. In certain glomerulopathies, including diabetic nephropathy, CD80 is expressed by podocytes and tubular cells and the renal excretion is increased [18, 20]. We have recently demonstrated the existence of podocyturia in Fabry disease, even in the absence of clinical nephropathy [24]
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