TABLE 1.

Individual cases of native kidney BK virus nephropathy included in our case series and systematic review of the literature

Reference	Age/ gender	Relevant medical history	Time to diagnosisa	Therapy attempted	Therapy effect	Dialysis	Outcome
HCT
Aksenova43	10 F	Allo-HCT	13 mo	Add IVIG, leflunomide, cidofovir, and ciprofloxacin.	Leflunomide/Cipro/IVIG simultaneously had no effect, but addition of cidofovir resulted din resolution of viremia and improved Cr		CKD
Bruno44	Nr	Allo-HCT	NR	Not reported	Not reported	N/A	Death
Burbach45	45 F	Allo-HCT	46 mo	Reduced immunosuppression.	Viremia remained elevated.	Yes	Death
Lekakis46	51 M	Allo-HCT	5 mo	Add leflunomide, cidofovir, and ciprofloxacin.	Viruria improved, Viremia not reported	Yes	Death
Maximova47	15 F	Allo-HCT	3 mo	Stopped immunosuppression	Viremia improved. Persistent viremia.	No	Death
O’Donnell48	41 F	Matched-unrelated donor HCT	30 mo	Add leflunomide.	Viremia not changed.	Yes	ESRD
Papanicolaou49	58 M	Allo-HCT	16 mo	Add brincidofovir	Viremia improved. Persistent viremia. Cr stable.	No	Death
Shapiro50	14 M	Unrelated cord blood transplant	1 mo	Reduced immunosuppression. Add cidofovir.	Received too few doses. Died of multiorgan failure shortly after 2nd dose of cidofovir.	No	Death
Sharma51	17 M	CML, haploidentical BMT complicated by GVHD	2 y	Add leflunomide and IVIG.	Viremia improved. Persistent viremia. Cr worsened.	No	Death
Sharma51	16 M	AML, Allo-HCT	4 mo	Diagnosed on autopsy		N/A	Death
Sharma51	58 M	CLL, Allo-HCT complicated by GVHD	24 mo	Add cidofovir. Add sirolimus due to GVHD.	Viremia improved. Persistent viremia. Cr stable.	No	CKD
Stracke52	28 F	Haploidentical T-cell depleted peripheral blood SCT	2 y	Add cidofovir	Viremia not improved. Cr not improved	Yes	ESRD
Van der Bij53	57 M	Allo-HCT with leukemic invasion	21 mo	Add leflunomide.	Cr worsened to ESRD, started on HD.	Yes	ESRD
Verghese54	10 M	unrelated cord blood transplant	3.5 y	Add cidofovir and ciprofloxacin.	No effect to cidofovir, resolution of viremia to cipro. Cr improved	No	CKD
Verghese54	13 M	Allo-HCT	2 y	Add cidofovir.	Viremia unchanged. Cr worsening.	No	Death
Vigil42	30 M	Allo-HCT	Approx. 4 y	Add ciprofloxacin.	Viremia worsened.	No	Death
Limaye55	41 M	Autologous Peripheral blood cell transfusion	6.2 y	Add cidofovir.	Viremia resolved.	Yes	ESRD
O’Donnell48	36 F	Auto-HCT	9 mo	Add leflunomide.	Viremia not changed.	Yes	Death
Sanchez-pinto56	10 F	Auto-HCT	5 mo	Add cidofovir and ciprofloxacin.	Viremia improved. Persistent viremia. Cr worsened.	Yes	Death
Hematologic malignancy
Filler57	10 M	ALL	3 y	Add IVIG	Viremia improved. Persistent viremia	No	CKD
Inaba58	5 F	ALL	21 mo	Reduce chemotherapy dose. Add IVIG, cidofovir, leflunomide	Viremia improved. Persistent viremia. Cr stable.	No	Unclear
Collett59	56 M	CLL	NR	Add IVIG and ciprofloxacin.	Viremia did not respond.	No	CKD
Mccrory60	73 M	CLL	1 y	Stopped IVIG, started leflunomide	Viremia improved. Persistent viremia.	No	CKD
Sangala61	72 M	CLL	19 mo	Short course of methylprednisolone, added IVIG and ciprofloxacin.	Cr worsened to ESRD requiring regular HD	Yes	Unclear
Sharma51	66 M	CLL	10 y	Add IVIG and cidofovir	Cr worsened to ESRD	Yes	ESRD
Sharma51	73 M	CLL	1 y	Add IVIG and cidofovir	Cr remained elevated.	No	CKD
De Silva62	6 mM	Cartilage-hair hypoplasia and Hodgkin’s disease	26 mo	Not reported		No	Death
Sharma51	53 M	Non-Hodgkin Lymphoma	4 y	Add cidofovir	Viremia improved. Persistent viremia.	No	Death
Shah (this paper)	34 M	Non-Hodgkin lymphoma		No specific therapy		Yes	Death
HIV
Bratt63	26 M	HIV: CD4 20 × 106/L	N/A	Diagnosed on autopsy		No	Death
Crum-Cianflone64	38 M	HIV: CD4 < 50*106/L but at time of renal failure was 0*106/L	N/A	No specific therapy	Required hemodialysis. Died 1 y later du to CNS lymphoma.	Yes	ESRD
Cubukcu-Dimopulo65	14 M	HIV: CD4 = 0	N/A	Diagnosed on autopsy		No	Death
Jung66	49 M	HIV: CD4 4 *106/L | VL 96800 copies/mL	N/A	No specific therapy	Worsened viremia. Cr worsened. Died of nonrenal reasons.	No	CKD
Manabe67	32 M	HIV: CD4 3 *106/ L | VL 4400 copies/mL	N/A	Diagnosed on autopsy		No	CKD
Mouratoff68	49 M	HIV: CD4 3 × 106/L	N/A	No specific therapy	Renal function improved with antiretrovirals for HIV, but worsened within 2 mo of biopsy.	No	CKD
Nebuloni69	31 M	HIV: CD4 0.01 × 109/L	N/A	No specific therapy	2 mo later, no clinical worsening.	No	CKD
Smith70	36 M	HIV: CD4 < 50 × 106/L	N/A	No specific therapy	Left hospital abruptly and died.	Yes	ESRD
Sukov71	43 M	HIV: CD4 2.0 × 109/L	N/A	No specific therapy	Became HD-dependent. No comment on viremia.	Yes	ESRD
Vallbracht10	27 M	HIV: n/a (autopsy)	N/A	Diagnosed on autopsy		No	Death
Solid organ transplant
Ali72	12 M	Heart transplant	21 mo	Reduce immunosuppression, add leflunomide and cidofovir	Effect unclear	No	CKD
Barber73	26 M	Heart transplant	18 mo	Reduce immunosuppression, add cidofovir	Viremia resolved with cidofovir 1 mg/kg	Yes	ESRD
Butts74	9 F	Heart transplant	8 y	Reduce immunosuppression, add leflunomide	Viremia reduced. Stable viremia.	No	CKD
Joseph75	60 M	Heart transplant	3 y	Reduce immunosuppression, add ciprofloxacin and IVIG	Viremia N/A. Cr worsened.	Yes	ESRD
Joseph75	43 M	Heart transplant	2 y	Reduce immunosuppression, add ciprofloxacin	Stable GFR. Viremia reduced. Stable viremia.	No	CKD
Limaye55	59 M	Heart transplant	6.8 y	Diagnosed on autopsy		Refused	Death
Lorica76	14 M	Heart transplant	6 mo	Reduce immunosuppression, add IVIG, cidofovir, and ciprofloxacin	Viremia reduced. Stable viremia.	Yes	Death
Maddirala77	54 M	Heart transplant	3.5 y	Reduce immunosuppression	Viremia N/A. Cr not improving.	Yes	Death
Menahem78	59 F	Heart transplant	16 mo	Reduce immunosuppression, add cidofovir	Viruria remained positive. GFR had no improvement	Yes	ESRD
Pereira79	5 F	Heart transplant	2 y	Reduce immunosuppression, add IVIG and cidofovir	Viral loads decreased at cidofovir 1 mg/kg but remained positive. Died of BKV rhombo-encephalomyelitis	Yes	Death
Sahney80	8 M	Heart transplant	10 mo	Reduce immunosuppression, add IVIG and cidofovir	Viremia reduced. Stable viremia.	Yes	ESRD
Schmid81	57 M	Heart transplant	29 mo	Reduce immunosuppression, add cidofovir	Cr improved. Viremia improved. Persistent viremia.	Yes	ESRD
Shah (this paper)	70 M	Heart transplant		Reduce immunosuppression	Cr worsened. Viremia improved. Persistent viremia.	Yes	Death
Dufek82	9 M	Lung transplant	2 y	Reduce immunosuppression, add cidofovir	Viremia persisted	Yes	Death
Egli83	72 F	Lung transplant	5 y	Reduce immunosuppression, add leflunomide	Viremia resolved. Cr improved.	No	CKD
Kuppachi84	63 M	Lung transplant	CKD at 2 y, biopsy at 4 y	Reduce immunosuppression, add cidofovir and leflunomide	Cr stabilized and improved. Persistent viremia	No	CKD
Schwarz85	40 M	Lung transplant	15 mo	Add cidofovir and leflunomide	Resolution of viremia but relapsed after therapy discontinued	Yes	ESRD
Sharma51	30 M	Lung transplant	2 y	Reduced immunosuppression	Cr worsened. Viremia improved. Viremia persistent.	No	CKD
Vigil42	70 M	Lung transplant	2 y	Reduce immunosuppression, add IVIG and leflunomide	Viremia improved. Viremia persistent.	No	CKD
Zeng86	59 M	Liver transplant	7 y	Not reported	Not reported	None reported	Not reported
Haririan87	54 M	Pancreas transplant	9 mo	Not reported	Not reported	No	CKD
Other
Go88	79 M	Prostate cancer	N/A	Diagnosed on nephrectomy	Not reported	No	CKD
Krystel-Whittemore89	55 M	Rheumatoid Arthritis	6 y	Reduce immunosuppression, add IVIG, ciprofloxacin, leflunomide	Viremia improved. Persistent viremia.	Temporary HD	CKD
Park90	34 M	None	N/A	Not reported	Not reported	No	CKD
Rosen91	6 M	Hyper-IGM	5 y	Not reported	Not reported	Yes	Death
Sharma51	66 M	Pulmonary tuberculosis	9 mo	Not reported	Not reported	Yes	Death

ALL, acute lymphoblastic leukemia; CKD, chronic kidney disease; CLL, chronic lymphocytic leukemia; ESRD, end stage renal disease; F, female; HCT, hematopoietic stem cell transplantation; HCT, hematopoietic cell transplant; HD, hemodialysis; HIV, human immunodeficiency virus; IVIG, intravenous IgG; M, male.

^aTime to diagnosis is defined as the time from a known immunologic inult to diagnosis of BKVN. In practice, this refers to the time from transplant/diagnosis of illness to diagnosis of BKVN. HIV was not included in this because the time to development and diagnosis of BKVN is not a meaningful metric when the underlying HIV can be well-controlled on antiretroviral therapy, yielding long time frames or highly variable times.