The overall objective of the proposed project is to develop a noninvasive diagnostic test that is predictive, diagnostic and prognostic of BK virus associated nephropathy. The primary hypothesis for the proposed investigation is that urinary cell messenger RNA (mRNA) profiles that include measurement of mRNA for BKV viral capsid protein 1 (VP1) are predictive, diagnostic and prognostic of BKV nephropathy.
The Specific Aims of the proposed investigation are:
Specific Aim 1. To document, in a large multi-center study, the validity of urinary cell BKV VP1 mRNA level as a highly sensitive (>90%) and specific (>90%) noninvasive diagnostic test for BKV nephropathy.
Specific Aim 2. To test the hypothesis, in a prospective cohort study, that urinary cell mRNA profiles, assessed at the time BKV nephropathy is diagnosed, predict renal allograft functional outcome.
Specific Aim 3. To evaluate BKV replication by measurement of BKV VP1 mRNA levels in sequential urine specimens and test whether elevations in BKV VP1 mRNA levels predict: (a) renal allograft function; and (b) the development of BKV nephropathy. BKV replication and development of BKV nephropathy will be explored in prospective cohort studies of not only adult but also pediatric recipients of renal allografts. In the pediatric study, we will also determine whether corticosteroid based immunosuppression is a risk factor for BKV replication and development of BKV nephropathy since the study cohort will be composed of pediatric patients enrolled in a NIAID sponsored multi-center randomized, parallel group trial comparing steroid based immunosuppression with steroid-free immunosuppression.
| Dadhania, Darshana; Snopkowski, Catherine; Muthukumar, Thangamani et al. (2013) Noninvasive prognostication of polyomavirus BK virus-associated nephropathy. Transplantation 96:131-8 |
| Hartono, Choli; Muthukumar, Thangamani; Suthanthiran, Manikkam (2010) Noninvasive diagnosis of acute rejection of renal allografts. Curr Opin Organ Transplant 15:35-41 |
| Dadhania, Darshana; Snopkowski, Catherine; Ding, Ruchuang et al. (2010) Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers. Transplantation 90:189-97 |
| Dadhania, Darshana; Snopkowski, Catherine; Ding, Ruchuang et al. (2008) Epidemiology of BK virus in renal allograft recipients: independent risk factors for BK virus replication. Transplantation 86:521-8 |
| Anglicheau, Dany; Suthanthiran, Manikkam (2008) Noninvasive prediction of organ graft rejection and outcome using gene expression patterns. Transplantation 86:192-9 |
| Muthukumar, Thangamani; Dadhania, Darshana; Ding, Ruchuang et al. (2005) Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N Engl J Med 353:2342-51 |
