A 52-year-old man comes to the physician for follow-up on cadaveric renal transplantation done 10 months ago for polycystic kidney disease. His postoperative course was complicated by 2 episodes of acute rejection and an episode of lower gastrointestinal bleeding. These events prompted revision of his immunosuppressive regimen, which now includes prednisone, tacrolimus, mycophenolate, and acyclovir. The patient has no new symptoms. His only other medical problem is diet-controlled type 2 diabetes mellitus.
His blood pressure is 122/70 mm Hg and pulse is 78/min. His BMI is 29 kg/m². There are no skin rashes. The spleen tip is not palpable. There is no lymphadenopathy.
Laboratory results are as follows:

Urine sediment analysis shows cellular casts. Cytology demonstrates atypical cells with intranuclear inclusions.
Which of the following is the most likely diagnosis?

Question

A 52-year-old man comes to the physician for follow-up on cadaveric renal transplantation done 10 months ago for polycystic kidney disease. His postoperative course was complicated by 2 episodes of acute rejection and an episode of lower gastrointestinal bleeding. These events prompted revision of his immunosuppressive regimen, which now includes prednisone, tacrolimus, mycophenolate, and acyclovir. The patient has no new symptoms. His only other medical problem is diet-controlled type 2 diabetes mellitus.
His blood pressure is 122/70 mm Hg and pulse is 78/min. His BMI is 29 kg/m². There are no skin rashes. The spleen tip is not palpable. There is no lymphadenopathy.
Laboratory results are as follows:

Urine sediment analysis shows cellular casts. Cytology demonstrates atypical cells with intranuclear inclusions.
Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

This patient most likely has human polyoma virus infection. There is a high prevalence of seropositivity of polyoma virus (eg, BK and JC) in the general population, but polyoma viruses cause disease only in immunosuppressed individuals. In renal transplant recipients, the BK form of polyoma virus produces tubulointerstitial nephritis and, less commonly, ureteric stenosis. The mean time of onset of BK infection is 10-15 months after transplantation. BK viral infection is most common in older men with type 2 diabetes mellitus and rejection episodes with significant immunosuppression. There are no characteristic clinical manifestations other than loss of renal function. The presence of cells with a single large basophilic intranuclear inclusion found on urine cytology suggests but does not prove BK infection. Serology is not as useful as many in the general population have antibodies against the virus. Renal biopsy findings can be similar to those in other viral infections (eg, cytomegalovirus). As a result, diagnosis requires renal biopsy showing characteristic cytopathology plus positive antibodies directed specifically against BK on immunohistochemistry tests. Biopsy sometimes misses the diagnosis, and at least 2 biopsy cores may be required in suspected patients. The primary treatment is reduction of immunosuppression. (Choice A) Allograft rejection can cause progressive renal dysfunction and may be difficult to differentiate clinically from BK infection. However, allograft rejection does not typically cause intranuclear inclusions on urine cytology. (Choice B) Diabetic nephropathy can recur after renal transplantation but usually presents several years after transplantation with significant proteinuria, which is not seen in this patient. (Choice C) Epstein-Barr virus may cause post-transplant lymphoproliferative disorder, which is due to both lymphoid and/or plasma cell proliferation in the transplanted organ/tissue. Patients may present with an infectious mononucleosis-like illness or nonspecific constitutional symptoms (eg, weight loss and fatigue) but usually do not have worsening renal function. (Choice E) The calcineurin inhibitors, including cyclosporine and tacrolimus, are potentially nephrotoxic. An acute nephrotoxicity is due to renal vasoconstriction and is often reversed by dosage reduction. A chronic form is due to vasculopathic changes in the kidney and is usually not reversible. Calcineurin inhibitors are not associated with intranuclear inclusions, and this patient's course is more characteristic of BK viral infection. Educational objective: BK polyoma virus presents in renal transplant recipients most commonly after rejection and significant immunosuppression. Patients typically develop tubulointerstitial nephritis with rising creatinine and the presence of intranuclear inclusions in urine cells. Definitive diagnosis requires renal biopsy plus positive immunohistochemistry tests using antibodies directed specifically against the BK virus. __________ References: The decade of polyoma BK-associated nephropathy: state of affairs. (http://www.ncbi.nlm.nih.gov/pubmed/19295303)

A 52-Year-Old Man Comes to the Physician for Follow-Up on Cadaveric