Polyomavirus allograft nephropathy

Polyomavirus allograft nephropathy is often an iatrogenic complication due to long term over immunosuppression and frequently leads to chronic kidney dysfunction and failure. Post renal transplantation, PVN has emerged as a major problem affecting up to 10% of all kidney grafts, most commonly within the first 6-18 months post surgery.

Cause

Polyomavirus nephropathy (PVN) is primarily caused by a productive intra-renal BK virus infection.

Stages

Recent advances in our understanding of the development and progression of PVN have resulted in the definition of clinically significant disease stages: A (early), B (florid) and C (sclerosing).

Signs and symptoms

Under immunocompromised conditions, however, the BK- and JC-polyomavirus strains can enter into “organ-destructive” replicative cycles and cause disease. Clinically significant infections/ disease caused by BK-viruses are primarily seen in the urinary tract, i.e., the bladder and kidneys, whereas JC-viruses mainly cause neurologic disorders, i.e., progressive multifocal leukoencephalopathy. Early reports that had linked productive infections with BK viruses to the development of ureteral necrosis and stenosis.

Diagnosis

In addition, improved multi-center cooperations are required in order to validate and standardize clinical tests more efficiently, such as quantitative PCR assays, decoy cell analyses including cell phenotyping, and urine electron microscopy as a non-invasive method to diagnose PVN.

Treatment

Unfortunately, treatment options are currently limited since highly specific anti-polyomavirus drugs are not available. Outcome of PVN is largely determined by three factors: (i) the disease stage at time of the initial diagnosis (ii) the duration of PVN with persistent, virally driven, pro-fibrotic tubulo-interstitial injury , and (iii) the extent of pre-existing graft damage, e.g., hypertension induced arterionephrosclerosis, structural calcineurin-inhibitor toxicity etc. Allograft rejection can contribute to graft demise. The ultimate therapeutic goal is to diagnose PVN early and to rapidly stop viral replication, thereby limiting tubular injury and preventing disease progression to irreversible scarring.

NIH genetic and rare disease info

• NIH info on Polyomavirus allograft nephropathy

Polyomavirus allograft nephropathy is a rare disease.