Abstract
Long-term kidney transplant outcomes have reached mild improvements recently. Parietal epithelial cells (PECs) are progenitor cells located along the Bowman’s capsule that can be isolated in urine, and display the capability to replace podocytes, but in certain situations cause glomerulosclerosis. In this study, a cohort of stable kidney transplant recipients with 6 months protocol biopsy was divided in two groups depending on the presence (uPEC+; n = 41) or absence (uPEC-; n = 25) of PECs in urine and followed for 2 years. No differences were found between groups at 6 months after transplantation considering clinical variables, alloimmune response, renal function, albuminuria and graft pathology. However, uPEC+ group showed increased podocyturia and a higher rate of proliferating PECs along the Bowman’s capsule, without concomitant enhancement of the CD44 pro-sclerotic activation marker. Accordingly, 2 years follow up evidenced poorer outcomes in the uPEC+ group with worse renal function, increased albuminuria, wider mesangial expansion and more severe IFTA. In summary, chronic allograft damage can progress in certain stable-supposed grafts by podocyte detachment and reactive PECs proliferation, being the uPEC presence a biomarker of this process. This damage-response regenerative process, if sustained in time, might fail in preserve the allograft function and histology. Our study raises new prospects to overcome current limits on long-term allograft results.
Highlights
Chronic kidney disease is a leading cause of morbidity and mortality nowadays, with a renal replacement therapy (RRT) prevalence of 924 patients per million population in Europe (Pippias et al, 2017)
In 41 out of 66 patients, it was possible to identify single flat body epithelial cells growing into clusters in a rose shape manner from the 1st week after plating, as Urinary PECs (uPECs) were undetectable by cytospins directly from urine due to its low number
Urinary CD133+CD24+ cells were negative for podocyte and tubular epithelial cell
Summary
Chronic kidney disease is a leading cause of morbidity and mortality nowadays, with a renal replacement therapy (RRT) prevalence of 924 patients per million population in Europe (Pippias et al, 2017). Kidney transplantation is the RRT option that offers the best outcomes in terms of life expectancy and quality of life (Wolfe et al, 1999). In this sense, new approaches are needed uPECs and Kidney Allograft Outcomes to improve graft function and survival especially considering long-term outcomes, where clinical advances have been subtle in the last years (Meier-Kriesche et al, 2004; Nankivell and Kuypers, 2011; Riella et al, 2016). The recently identified progenitor cell population surrounding the Bowman’s capsule displays a multipotent capacity of differentiation into kidney specific cells terminally differentiated (podocytes and tubular cells), which are characterized by the coexpression of two species- specific markers, CD133 and CD24 (Sagrinati et al, 2006). These Parietal Epithelial Cells (PECs) exhibit the capacity to ameliorate acute kidney damage (Lasagni et al, 2015), but in certain conditions these cells might contribute to crescent formation (Sicking et al, 2012) or glomerulosclerosis by characteristically de novo expression of CD44 (Smeets et al, 2011) or by undergoing epithelial to mesenchymal transition (Naito et al, 2014)
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