ESPN 50th Annual Meeting

ESPN 2017


 
BK-VIRUS NEPHRITIS IN PEDIATRIC PATIENT AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: SERIAL OF CASES
MARINA AKSENOVA 1 MARINA AKSENOVA 2 VERA TSETLINA 2 ELENA GUTOVSKAYA 2 NADEJDA SMIRNOVA 2 ANNA MITROFANOVA 2 DMITRY BALASHOV 2 ALEXANDER MASCHAN 2

1- SCIENTIFIC RESEARCH CLINICAL INSTITUTE OF PEDIATRICS, N.I.PIROGOV’ NATIONAL RUSSIAN MEDICAL UNIVERSITY OF MOSCOW
2- DMITRY ROGACHEV FEDERAL SCIENTIFIC-CLINICAL CENTER OF CHILDRENS OF HEMATOLOGY, ONCOLOGY AND IMMUNOLOGY
 
Introduction:

 Renal dysfunction in hematopoietic stem cell transplantation (HSCT) recipient traditionally has been attributed to use of nephrotoxic drug. BK-virus nephritis (BKVN) can remain undiagnosed in these patients due to lack of screening for BK-infection and  to its nonspecific clinical picture. 

Material and methods:

 The cases of BKVN after HSCT were reviwed.

Results:

 Pt 1. Six-year-old girl with multilinear myelodysplasia presented with the rising of serum creatinine (from 58  to 120 µmol/l ) on 13 mo after HSCT. One month before renal dysfunction she had pulmonitis of unknown etiology. The girl had stem cell transplant’s hypofunction and secondary immunodeficiency and was treating with Methotrexate (0,6 mg/kg/week),  Cyclophosphamide (200 mg/m2/week) because of chronic graft-versus-host disease (GVHD). Urinalysis and renal US were normal. BK-virus PCR analysis revealed 6,7 x106 copies/ml in urine. A renal biopsy showed tubulointerstitial injuary with many tubular intranuclear inclusions and positive immunostainig for SV-40. Immunosuppression was discontinued, therapy with IVIG 1g/kg, Cidofovir 0,5 mg/kg/week, Leflunomide 10 mg/day was started.  Despite BK eradication there was no improvement in renal function after 2 mo of treatment. To date she has stable renal  insufficiency: Crs=128 µmol/l,  eGFR =26 ml/min.

Pt 2. Eight months after HSCT due to refractory T-cell acute lymphoblastic leukemia ten-year-old boy had an episode of encephalitis with extrapontial myelinosis (etiology?) and serum creatinine level increasing (from 38 to 180 µmol/l). He received Prednisone 2mg/kg/day and Prograf 0,015 mg/kg/day because of GVHD. Urine BK-virus titer was 2x106 copies/ml. A renal biopsy revealed tubulointerstitial nephritis with positive immunostainig for SV-40. Immunosuppression was discontinued, therapy with IVIG 1g/kg, Leflunomide 10 mg/day, Ciprofloxacin 20 mg/kg/day was started.  During 2 years of observation the boy had stable renal dysfunction: eGFR =60 ml/min.

Pt 3. The 22-year boy with acute myeloblastic leukemia (M1/M2) presented with renal impairment: Cr s rose from 54 to 202 µmol/l 12 months after of HSCT. He was on treatment with Prednisone 0,5 mg/kg/day, CyclosporineA 200 mg/day and Bortezomib (Velcade) 0,4 mg/kg/week due to skin form of GVHD. The boy had secondary immunodeficiency and recurrent CMV-virus infection. The renal dysfunction was preceded by hemorrhagic cystitis. Urine BK-virus titer was 12x103 copies/ml, the renal biopsy confirmed BKVN. Therapy with IVIG 1g/kg, Cidofovir 0,5 mg/kg/week, Leflunomide 10 mg/day and Ciprofloxacin 250 mg/day was started. There was no recovery of renal function; the boy had stable eGFR about 30-35 ml/min during 2 years of observation.

Conclusions:

 We suppose that the actual incidence of BKVN after HSCT is much higher than what is commonly thought. Our clinical cases demonstrate that BK-virus screening and renal biopsy would be performed in all non-renal transplant and immunosuppressed patients with unexplained rising of serum creatinine. These patients may benefit from early detection and treatment of BKVN and modification of immunosuppressive therapy.