|Year : 2020 | Volume
| Issue : 2 | Page : 162-165
Posttransplant thrombotic microangiopathy: A rare cause
Chaitanya Siva Marupudi, Balasubramanian Thoppalan, Venkataman Ramudu
Department of Nephrology, Kilpauk Medical College, Chennai, Tamil Nadu, India
|Date of Submission||13-Feb-2020|
|Date of Acceptance||17-May-2020|
|Date of Web Publication||06-Jul-2020|
Dr. Chaitanya Siva Marupudi
Room No. 40 KMC UG Men's Hostel, Kilpauk Medical College, Chennai - 600 010, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Parvovirus B19 is a common cause of aplastic anemia in immunosuppressed patients. However, renal involvement in cases of B19 infection is rare. The clinical presentation and histologic pattern of renal involvement due to parvovirus B19 infection has been described only in a few case reports. We report a patient with thrombotic microangiopathy (TMA) of graft kidney presumably secondary to B19 infection. The patient presented with severe anemia and allograft dysfunction following kidney transplantation. Kidney allograft biopsy was suggestive of TMA, and acute B19 infection was confirmed by the detection of viral DNA in the patient's serum. The patient had complete recovery following high-dose intravenous immunoglobulin therapy and reduction of immunosuppression.
Keywords: Parvovirus B19, renal transplantation, thrombotic microangiopathy
|How to cite this article:|
Marupudi CS, Thoppalan B, Ramudu V. Posttransplant thrombotic microangiopathy: A rare cause. Indian J Transplant 2020;14:162-5
| Introduction|| |
Parvovirus is a small, single-stranded DNA virus belonging to the Parvoviridae family. Parvovirus was first identified in 1975 and linked to human disease in 1981. Currently, three genotypes of parvovirus have been identified (B19, LaLi, and V9), of these, B19 is the prototype strain causing most of the infections in humans.,, Infection is common and occurs worldwide, with 70%–85% of adults showing serologic evidence of past infection., Infection is usually transmitted by inhalation of the virus in aerosol droplets, but can also be transmitted vertically from mother to fetus  and less commonly through transfusion of blood products. Reactivation of latent infection or transmission from donor is common in solid-organ transplant recipients.
Immunocompetent individuals commonly present with nonspecific prodromal symptoms, rash of erythema infectiosum and/or arthralgias, and transient aplastic crisis in individuals with hematologic abnormalities (e.g., sickle cell disease, hereditary spherocytosis, and iron-deficiency anemia). In immunocompetent individuals, numerous case reports have described the onset of nephritis or nephrotic syndrome after parvovirus infection in the form of postinfectious glomerulonephritis, collapsing glomerulopathy, and focal segmental glomerulosclerosis (FSGS).
Wirenga et al. reported patients with sickle cell disease who developed glomerulonephritis after aplastic crisis due to B19 infection. Renal biopsies showed segmental proliferative glomerulonephritis in four patients and FSGS in one patient. To characterize the potential association between B19 infection and glomerular disease, native kidney biopsies of 44 patients with different glomerular diseases (collapsing glomerulopathy and idiopathic FSGS, membranous nephropathy, minimal change nephropathy, and controls) were tested by Tanawattanacharoen et al. for B19 genome using polymerase chain reaction (PCR) and found that patients with collapsing glomerulopathy and FSGS had the highest prevalence of parvovirus B19 compared with other renal diseases, although the difference was marginally significant. In a similar study, Moudgil et al. found a significantly higher prevalence of B19 DNA in renal biopsies from patients with collapsing glomerulopathy (78%), compared with other nephropathies (idiopathic FSGS 22%, HIV-associated collapsing glomerulopathy 16%, and controls 26%).
The first case of parvovirus B19 infection in a kidney transplant recipient was published in 1986. The most common consequence of parvovirus infection in the renal transplant recipient is pure red cell aplasia (PRCA). Parvovirus exhibits trophism for the involvement of erythroid precursor cells in bone marrow, and these are the only cells that can support productive infection. This is due to the presence of P blood group antigen, the cellular receptor for parvovirus in higher concentrations on these cells. P antigen is also found to a lesser extent on other cell types, including endothelial cells, cardiomyocytes, megakaryocytes, and placental trophoblast cells, however, infection of these cells fails to produce infectious virus but contributes to disease through the expression of nonstructural (NS1) protein, which can induce cellular apoptosis in both permissive and nonpermissive cells.
Renal involvement can present as transient allograft dysfunction, acute allograft rejection, or collapsing glomerulopathy. Rarely, cases of thrombotic microangiopathy (TMA) have also been documented. Here, we report a case of de novo TMA due to parvovirus infection after kidney transplantation.
| Case Report|| |
A 35-year-old Indian female with end-stage renal disease from reflux nephropathy was on twice-weekly hemodialysis for 2 years. She received a kidney allograft from her mother in December 2018. Steroid induction and triple immunosuppression were used. The perioperative period was uneventful. She was discharged at postoperative day 10 with serum creatinine (Cr) at 1.2 mg/dl and hemoglobin at 9.2 g/dl. The medications at discharge were tacrolimus 4 mg/day (tacrolimus trough concentration 4.6 ng/ml), mycophenolate mofetil (MMF) 1.5 g/day, prednisolone 30 mg/day, co-trimoxazole, and valganciclovir. On follow-up, prednisolone dose was tapered, and tacrolimus dose increased to 5 mg/day (trough concentration 5.3 ng/ml).
At 3 months posttransplant, she presented with easy fatigability and breathlessness on exertion for 2 weeks. Her physical examination was unremarkable, except for pallor. As initial investigations revealed severe anemia of hemoglobin 5.4% g, she was admitted for further evaluation. Her laboratory investigations are shown in [Table 1], and the clinical course is shown in [Table 2]. She had severe anemia with reticulocytopenia, and peripheral smear showed no evidence of hemolysis or abnormal cells. PRCA was suspected as other common causes of anemia were ruled out. Bone marrow aspiration showed normocellular marrow with erythroid hypoplasia suggestive of PRCA.
While being evaluated for the cause of anemia, she developed graft dysfunction. Her urine analysis was positive for blood and protein. She tested negative for hepatitis B, hepatitis C, and HIV. Graft ultrasound and Doppler showed a regular morphology and perfusion, with a normal vascular resistive index (<0.6). A renal biopsy was performed for diagnostic purposes, which showed endothelial swelling with closure of glomerular capillary tuft and single myocyte necrosis, suggestive of TMA [Figure 1] and [Figure 2]. Kidney biopsy showed no features of acute rejection or calcineurin inhibitor toxicity. De novo postkidney transplant TMA was diagnosed, and the cause was evaluated. Cytomegalovirus DNA PCR was negative, but parvovirus B19 DNA PCR was positive. Based on the temporal association between clinical symptoms, graft dysfunction, onset of TMA, and isolation of viral genome from the blood, we diagnosed the patient with TMA secondary to parvovirus B19 infection. The diagnosis was confirmed by demonstrating a parvovirus antigen by immunofluorescence staining in the renal biopsy specimen.
|Figure 1: Hematoxylin and eosin stain: The glomerulus on the right shows endothelial swelling and closure of the glomerular capillary tuft|
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|Figure 2: Massons trichrome: single myocyte necrosis seen in the small artery|
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Blood was transfused, co-trimoxazole was stopped, and the MMF dose was reduced to 1 g/day. In view of severe anemia and graft dysfunction, intravenous immunoglobulin was administered at a dose of 400 mg/kg for 5 days. She had gradual improvement in graft function and anemia over 2 weeks. Currently, she is on follow-up with a serum Cr of 1.2 mg/dl and hemoglobin of 11 g/dl; her repeat parvovirus DNA PCR was negative.
| Discussion|| |
TMA after kidney transplantation can be de novo or recurrent. De novo TMA can affect 3–14% of kidney transplant recipients, and TMA recurs in 25%–50% of patients who have TMA as a cause of end-stage renal disease. Nearly all patients with recurrent TMA have a complement-mediated disease that produce both the pretransplant TMA and recurrence after transplantation. De novo TMA may be due to any of the etiologies that cause TMA in the general population or may be related to the transplantation. Causes of TMA that are common among transplant recipients include immunosuppressive drugs, ischemia–reperfusion injury, viral infections, and antibody-mediated rejection. Viral infections that have been implicated as a cause of de novo TMA are HIV, parvovirus B19, and cytomegalovirus. These viruses are capable of directly infecting endothelial cells, causing endothelial cell dysfunction, capillary thrombosis, and glomerular death.
In a case series published by Murer et al., B19 infection was implicated in four cases of renal allograft dysfunction, all of which had histologic findings of TMA. Like our case, the renal dysfunction was simultaneous or within days of an aplastic crisis. The viral genome was isolated by PCR in all renal biopsies and in the peripheral blood of those tested. One patient was treated with intravenous immunoglobulin (IVIG), but the others improved spontaneously with gradual resolution of anemia (after 22 days to 12 months) and recovery of graft function (22–110 days after the onset).
There are no established guidelines for screening of B19 infection in organ transplant recipients. However, screening may be useful in prospective transplant recipients on hemodialysis with moderate-to-severe anemia for whom other causes of anemia have been excluded. Diagnosis in a posttransplant scenario is established by isolating the viral genome from blood or renal tissue. Serological testing may not be useful due to poor antibody response in immunosuppressed individuals.
Our patient was treated with IVIG, and reduction in immunosuppressive medication and showed improvement in both anemia and graft dysfunction by 2 weeks of therapy. Various regimens of IVIG have been proposed, but evidence based on controlled studies is currently lacking.
The role of parvovirus infection as a trigger of glomerular disease has yet to be firmly established but deserves further attention because it may have implications in prevention strategies and treatment. B19 parvovirus infection should be taken into consideration as a possible cause of de novo TMA of renal grafts. The temporal association between B19-related hematologic abnormalities and the onset of graft TMA, the isolation of the viral genome from blood or renal specimens, and the endothelial trophism of the virus suggest that a cause-and-effect relationship could exist between B19 infection and posttransplant TMA.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]