Presence of Urinary Haufen Accurately Predicts Polyomavirus Nephropathy

Abstract

There are no accurate, noninvasive tests to diagnose BK polyomavirus nephropathy, a common infectious complication after renal transplantation. This study evaluated whether the qualitative detection of cast-like, three-dimensional polyomavirus aggregates ("Haufen") in the urine accurately predicts BK polyomavirus nephropathy. Using negative-staining electron microscopy, we sought Haufen in 194 urine samples from 139 control patients and in 143 samples from 21 patients with BK polyomavirus nephropathy. Haufen detection was correlated with pathology in concomitant renal biopsies and BK viruria (decoy cell shedding and viral load assessments by PCR) and BK viremia (viral load assessments by PCR). Haufen originated from renal tubules containing virally lysed cells, and the detection of Haufen in the urine correlated tightly with biopsy confirmed BK polyomavirus nephropathy (concordance rate 99%). A total of 77 of 143 urine samples from 21 of 21 patients with BK polyomavirus nephropathy (disease stages A-C) contained Haufen, and during follow-up (3 to 120 wk), their presence or absence closely mirrored the course of renal disease. All controls were Haufen-negative, however, high viremia or viruria were detected in 8% and 41% of control samples, respectively. statistics showed fair to good agreement of viruria and viremia with BK polyomavirus nephropathy or with Haufen shedding and demonstrated an excellent agreement between Haufen and polyomavirus nephropathy ( 0.98). Positive and negative predictive values of Haufen for BK polyomavirus nephropathy were 97% and 100%, respectively. This study shows that shedding of urinary Haufen and not BK viremia and viruria accurately mark BK polyomavirus nephropathy. It suggests that the detection of Haufen may serve as a noninvasive means to diagnose BK polyomavirus nephropathy in the urine.

Incidence and Outcomes of BK Virus Allograft Nephropathy among ABO- and HLA-Incompatible Kidney Transplant Recipients

“…In the context of incompatible transplantation, a cohort at increased risk for rejection, the ability to clearly differentiate between the two histopathologic diagnoses is crucial. In a retrospective analysis of compatible kidney transplant recipients, Singh et al (35) reported excellent ability of cast-like, three-dimensional polyomavirus aggregates (termed Haufen crystals) to qualitatively predict the presence of BKVAN (97% and 100% positive and negative predictive values), a putative future option.…”

BK Virus in Solid Organ Transplant Recipients

“…Other markers associated with PyVAN are BKV VP1 mRNA of >6 log copies/ng total urine RNA (64) or the detection urine PyV aggregates by electron microscopy (65). PyVAN (42,44,53,66 (83,84), while others report no demonstrable benefit (54,(85)(86)(87).…”

The BK virus in renal transplant recipients—review of pathogenesis, diagnosis, and treatment

“…Haufen, a recently described entity, are discrete cast-like three-dimensional viral aggregates detectable by negative staining electron microscopy. The detection of Haufen aggregates was reported to be associated with BKVN to a high degree of sensitivity and specificity, such that PPV and NPV are both above 97% [49,50]. These initial studies need to be confirmed in larger series.…”