Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation

Abstract

BackgroundCollapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG. Despite significant advances, explaining such genetic and immune/infectious associations with causative mechanisms and supporting evidence has proven challenging.Case presentationWe report the case of a healthy (HIV-negative) pregnant 36 year-old Caribbean-American woman who presented with nephrotic syndrome and fetal demise in the setting of acute parvovirus B19 infection. A series of three renal biopsies and rapid clinical course showed progression from significant podocyte injury with mild light microscopy findings to classic viral-associated CG to ESRD in less than 3 months. Genetic analysis revealed two APOL1 G1 risk alleles.ConclusionsThis is the first published case report of CG in the setting of acute parvovirus infection in a patient with two APOL1 risk allelles, and parvoviral proteins identified in renal epithelium on kidney biopsy. These findings support the causative role of parvovirus B19 infection in the development of CG on the background of APOL1 genetic risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0330-7) contains supplementary material, which is available to authorized users.

Collapsing Lesions and Focal Segmental Glomerulosclerosis in Pregnancy: A Report of 3 Cases

“…The incidence of collapsing FSGS in pregnancy is not known; we were able to find only 2 such reports, with 2 other reports (4 cases) in which collapsing lesions were superimposed on thrombotic microangiopathy (TMA). [28][29][30][31] The first 2 cases were reported in the first trimester of pregnancy (6 and 8 weeks' gestation). In the first case, systemic lupus erythematosus was present, and in the second, a viral infection and genetic predisposition coexisted.…”

“…In the first case, systemic lupus erythematosus was present, and in the second, a viral infection and genetic predisposition coexisted. 28,29 In the 4 additional cases, collapsing glomerulosclerosis was associated with TMA; these patients developed acute kidney injury in the postpartum period. 30,31 The association with TMA [31][32][33] is intriguing.…”

Post‐infectious acute glomerulonephritis with podocytopathy induced by parvovirus B19 infection

“…Collapsing glomerulopathy usually shows therapy resistance and a worse renal prognosis compared to other histological variants of focal segmental glomerulosclerosis . Although there have been only three cases of collapsing glomerulopathy due to HPVB19 with clinical courses described in the literature, most patients revealed acute onset and heavy proteinuria with persistent HPVB19 infection. All the cases progressed to end stage renal disease despite intensive therapy of prednisolone and intravenous immunoglobulin .…”

“…Although there have been only three cases of collapsing glomerulopathy due to HPVB19 with clinical courses described in the literature, most patients revealed acute onset and heavy proteinuria with persistent HPVB19 infection. All the cases progressed to end stage renal disease despite intensive therapy of prednisolone and intravenous immunoglobulin . The reason why our case showed good responsiveness to intense immunosuppressive therapy remains unclear; however, various patient background factors (age, gender, APOL1 risk alleles, and sickle cell disease), persistent HPVB19 infection, or the severity of podocyte injury may contribute to the renal prognosis of podocytopathy induced by HPVB19 infection.…”

Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.

“…Renal presentation was mostly post-infectious GN, but collapsing focal segmental glomerulosclerosis (FSGS), membrano-proliferative GN, and thrombotic microangiopathy have also been reported. (4)(5)(6)(7)(8) Extra-hematological and extra-renal signs can vary from mild or moderate (rash, symmetric arthralgia or arthritis) to severe manifestations (myocarditis, pericarditis, cryoglobulinemic vasculitis, lymphoproliferation), depending on the age, comorbidity, and immunological status of the host (9).…”