Archetype JC Polyomavirus (JCPyV) Prevails in a Rare Case of JCPyV Nephropathy and in Stable Renal Transplant Recipients With JCPyV Viruria.

Background: JC polyomavirus (JCPyV) is reactivated in approximately 20% of renal transplant recipients, and it may rarely cause JCPyV-associated nephropathy (JCPyVAN). Whereas progressive multifocal leukoencephalopathy of the brain is caused by rearranged neurotropic JCPyV, little is known about viral sequence variation in JCPyVAN owing to the rarity of this condition. Methods: Using single-molecule real-time sequencing, characterization of full-length JCPyV genomes in urine and plasma samples from 1 patient with JCPyVAN and 20 stable renal transplant recipients with JCPyV viruria was attempted. Sequence analysis of JCPyV strains was performed, with emphasis on the noncoding control region, the major capsid protein gene VP1, and the large T antigen gene. Results: Exclusively archetype strains were identified in urine from the patient with JCPyVAN. Full-length JCPyV sequences were not retrieved from plasma. Archetype strains were found in urine samples from 19 stable renal transplant recipients, with JCPyV quasispecies detected in 5 samples. In a patient with minor graft dysfunction, a strain with an archetype-like noncoding cont rol region was discovered. Individual point mutations were detected in both VP1 and large T antigen genes. Conclusions: Archetype JCPyV was dominant in the patient with JCPyVAN and in stable renal transplant recipients. Archetype rather than rearranged JCPyV seems to drive the pathogenesis of JCPyVAN.

TGF-ß1 expression in kidney allograft protocol biopsies during cyclosporine A therapy.

BACKGROUND: TGF-ß1 expression has been described to increase along with time from transplantation and has also been linked to allograft dysfunction and toxic effects of cyclosporine. Our aim was to correlate intragraft TGF-ß1 expression with cyclosporine exposure after kidney transplantation.
 METHODS: Altogether 53 kidney allograft protocol biopsies from 42 patients on a low-dose cyclosporine-based regimen obtained at 3, 6, and 12 months were classified according to Banff and the chronic allograft damage index (CADI). TGF-ß1 expression in tubules, glomeruli, vessels, and inflammatory cells was semi-quantitatively scored and correlated with cyclosporine concentrations (C0 and C2), CADI, and graft function. 
 RESULTS: TGF-ß1 expression was mildly increased along time from transplantation, but the results were not statistically significant. TGF-ß1 expression was neither related to CADI nor to the use of ACE inhibitors/ARB. TGF-ß1 expression in the kidney was not correlated with C0 or C2 levels or kidney graft function during follow-up. 
 CONCLUSION: In protocol biopsies from patients on low-dose cyclosporine regimen, expression of TGB-ß1 was not significantly increased along time since transplantation, and did not correlate with cyclosporine exposure. Our findings suggest that the toxic effects of low-dose cyclosporine on TGF-ß expression may be milder than previously thought.