Polyomavirus-associated nephropathy

Table 1 Polyomaviruses detected in humans and involved in the pathogenesis of polyomavirus-associated nephropathy

Virus	Host	Clinical diseases
BKV	Human	PVAN in renal transplantation
		Hemorrhagic cystitis in bone marrow transplantation
JCV	Human	Progressive multifocal leukoencephalopath
		PVAN in renal transplantation
SV-40	Non-human primate	Unknown; PVAN in renal transplantation?

PVAN: Polyomavirus-associated nephropathy; BKV: BK virus; JCV: JC virus.

Table 2 Determinants in the development of polyomavirus-associated nephropathy

Determinants
Patient-related	Age > 50 yr
	Male gender
	Comorbidities (diabetes mellitus)
	Negative serostatus before transplantation
Organ-related	Degree of HLA mismatching
	Prior rejection episodes
	Renal injury
	Latent infection load
Viral-related	NCCR rearrangements
	Genotype
	Viral fitness
Immunity-related	Intense triple immunosuppression (calcineurin-inhibitor, antiproliferative agent, steroid)
	Rejection and anti-rejection treatment (anti-lymphocyte preparations, iv steroid boluses)
	Positive serostatus of donor
	Low number of BKV-specific T-cells

NCCR: Noncoding control region; BKV: BK virus.

Table 3 Algorythm for the virological monitoring of polyomavirus BK replication in renal transplantation[49]

Assay	Notes	Timing - intervention
Screening	Positive screening test (possible PVAN)	Every 3 mo up to 2 yr post-transplantation or in case of allograft dysfunction or when renal biopsy is performed
Urine cytology (decoy cells) or urine DNA load
Adjunctive quantitative tests (threshold)	Presumptive PVAN	Pre-emptive reduction of immunosuppression
Urine DNA load > 107 copies/mL or plasma DNA load > 104 copies/mL
Allograft biopsy	Definitive diagnosis of PVAN
Monitoring of response to treatment		Every 2-4 wk
Urine DNA load decreasing or plasma DNA load decreasing
Serum creatinine
	Negative monitoring test (resolved PVAN)

PVAN: Polyomavirus-associated nephropathy.

Table 4 Recommended treatment of polyomavirus-associated nephropathy by reduction or switching of immunosuppression[49]

Switching	Decreasing
Tacrolimus → Cyclosporine A (trough levels 100-150 ng/mL)	Tacrolimus (trough levels < 6 ng/mL)
Mycophenolate mofetil → Azathioprine (dose ≤ 100 mg/d)	Cyclosporine A (trough levels 100-150 ng/mL)
Tacrolimus → sirolimus (trough levels < 6 ng/mL)	Mycophenolate mofetil dose ≤ 1 g/d
Mycophenolate mofetil → sirolimus (trough levels < 6 ng/mL)	Cyclosporine A (trough levels 100-150 ng/mL)
Mycophenolate mofetil → leflunomide