Increase of Proliferating Renal Progenitor Cells in Acute Tubular Necrosis Underlying Delayed Graft Function

Hyperoxaluria is an important and underrecognized cause for allograft dysfunction and loss after transplantation. It is potentially treatable if recognized in a timely fashion. Research is ongoing to expand the array of therapeutic options available to treat this. We present a case of a 59-year-old gentleman who underwent deceased donor renal transplantation that was complicated by delayed graft function necessitating continuation of renal replacement therapy. His initial biopsy showed extensive acute tubular necrosis with associated peritubular capillaritis and interstitial nephritis and oxalate crystals in several tubules. Despite receiving methylprednisolone to treat moderate acute cellular rejection, he remained dialysis dependent with minimal urine output. An interval renal allograft biopsy revealed residual acute tubular necrosis with extensive oxalate crystals now visible in many tubules. His plasma oxalate level was concurrently elevated to 19.3 μmol/L (reference range ≤ 1.9 μmol/L). He commenced calcium citrate to manage his hyperoxaluria and ultimately became dialysis independent at 3 weeks after transplantation. This case provides an important example of accelerated oxalate nephropathy as an underappreciated contributor to delayed graft function after renal transplantation. Our accompanying discussion provides an update on current therapeutic measures for managing this challenging condition.

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Conversion from cyclosporine to tacrolimus in renal allograft recipients with delayed graft function from severe acute tubular necrosis

Transplantation Proceedings ◽

10.1016/s0041-1345(00)01403-2 ◽

2000 ◽

Vol 32 (7) ◽

pp. 1714-1715

Author(s):

H.J Jang ◽

S.C Kim ◽

D.J Han

Keyword(s):

Acute Tubular Necrosis ◽

Renal Allograft ◽

Graft Function ◽

Delayed Graft Function ◽

Tubular Necrosis

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BMP-2 induces a profibrotic phenotype in adult renal progenitor cells through Nox4 activation

AJP Renal Physiology ◽

10.1152/ajprenal.00328.2011 ◽

2012 ◽

Vol 303 (1) ◽

pp. F23-F34 ◽

Cited By ~ 17

Author(s):

Simona Simone ◽

Carmela Cosola ◽

Antonia Loverre ◽

Marica Cariello ◽

Fabio Sallustio ◽

...

Keyword(s):

Nadph Oxidase ◽

Protein Expression ◽

Progenitor Cells ◽

Smooth Muscle Actin ◽

Graft Function ◽

Renal Progenitor Cells ◽

Bmp Receptors ◽

Renal Progenitor

Adult renal progenitor cells (ARPCs) isolated from the human kidney may contribute to repair featuring acute kidney injury (AKI). Bone morphogenetic proteins (BMPs) regulate differentiation, modeling, and regeneration processes in several tissues. The aim of this study was to evaluate the biological actions of BMP-2 in ARPCs in vitro and in vivo. BMP-2 was expressed in ARPCs of normal adult human kidneys, and it was upregulated in vivo after delayed graft function (DGF) of renal transplantation, a condition of AKI. ARPCs expressed BMP receptors, suggesting their potential responsiveness to BMP-2. Incubation of ARPCs with this growth factor enhanced reactive oxygen species (ROS) production, NADPH oxidase activity, and Nox4 protein expression. In vivo, Nox4 was localized in BMP-2-expressing CD133+ cells at the tubular level after DGF. BMP-2 incubation induced α-smooth muscle actin (SMA), collagen I, and fibronectin protein expression in ARPCs. Moreover, α-SMA colocalized with CD133 in vivo after DGF. The oxidative stimulus (H2O2) induced α-SMA expression in ARPCs, while the antioxidant N-acetyl-cysteine inhibited BMP-2-induced α-SMA expression. Nox4 silencing abolished BMP-2-induced NADPH oxidase activation and myofibroblastic induction. We showed that 1) ARPCs express BMP-2, 2) this expression is increased in a model of AKI; 3) BMP-2 may induce the commitment of ARPCs toward a myofibroblastic phenotype in vitro and in vivo; and 4) this profibrotic effect is mediated by Nox4 activation. Our findings suggest a novel mechanism linking AKI with progressive renal damage.

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