Case Report: CMV-Associated Congenital Nephrotic Syndrome

Abstract

Background: Congenital nephrotic syndrome, historically defined by the onset of large proteinuria during the first 3 months of life, is a rare clinical disorder, generally with poor outcome. It is caused by pathogenic variants in genes associated with this syndrome or by fetal infections disrupting podocyte and/or glomerular basement membrane integrity. Here we describe an infant with congenital CMV infection and nephrotic syndrome that failed to respond to targeted antiviral therapy. Case and literature survey highlight the importance of the “tetrad” of clinical, virologic, histologic, and genetic workup to better understand the pathogenesis of CMV-associated congenital and infantile nephrotic syndromes.Case Presentation: A male infant was referred at 9 weeks of life with progressive abdominal distention, scrotal edema, and vomiting. Pregnancy was complicated by oligohydramnios and pre-maturity (34 weeks). He was found to have nephrotic syndrome and anemia, normal platelet and white blood cell count, no splenomegaly, and no syndromic features. Diagnostic workup revealed active CMV infection (positive CMV IgM/PCR in plasma) and decreased C3 and C4. Maternal anti-CMV IgG was positive, IgM negative. Kidney biopsy demonstrated focal mesangial proliferative and sclerosing glomerulonephritis with few fibrocellular crescents, interstitial T- and B-lymphocyte infiltrates, and fibrosis/tubular atrophy. Immunofluorescence was negative. Electron microscopy showed diffuse podocyte effacement, but no cytomegalic inclusions or endothelial tubuloreticular arrays. After 4 weeks of treatment with valganciclovir, plasma and urine CMV PCR were negative, without improvement of the proteinuria. Unfortunately, the patient succumbed to fulminant pneumococcal infection at 7 months of age. Whole exome sequencing and targeted gene analysis identified a novel homozygous, pathogenic variant (2071+1G>T) in NPHS1.Literature Review and Discussion: The role of CMV infection in isolated congenital nephrotic syndrome and the corresponding pathological changes are still debated. A search of the literature identified only three previous reports of infants with congenital nephrotic syndrome and evidence of CMV infection, who also underwent kidney biopsy and genetic studies.Conclusion: Complete workup of congenital infections associated with nephrotic syndrome is warranted for a better understanding of their pathogenesis (“diagnostic triad” of viral, biopsy, and genetic studies). Molecular testing is essential for acute and long-term prognosis and treatment plan.

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

“…Genetic studies confirmed Finnish-type CNS in three out of the remaining five patients with CNS and cCMV [41,51]. Several articles reporting infants with CNS were excluded after the full-text review due to the diagnosis of CMV infection being made beyond 3 weeks of age [79][80][81][82][83][84][85][86][87][88][89][90][91][92][93]; additionally, four infants in the Chen case series were excluded for the same reason [51]. Overall, 21 patients with concomitant CMV infection (cCMV, n = 5; CMV infection diagnosed beyond 3 weeks of age, n = 16) and CNS have been reported (Table 5).…”

Is Cytomegalovirus a Partaker or a By-stander in Congenital Nephrotic Syndrome? : A novel mutation update.

“…However the literature portrays occasional studies including the study by Jacob etal and Chen etal, where anti-CMV therapy was instituted in CMV associated CNS. 2,3 From India, Murugananth et al, describes the first case of isolated renal involvement of CMV infection in an infant who presented with reno-megaly, transient renal failure and renal biopsy with CMV inclusions. 4 Similarly, our second case is also a sole renal manifestation of CMV infection.…”

“…1 Till 2020, only four completely worked up CMV IgM positive CNS cases were reported globally signifying the low incidence of detection. 2 We present the case of two infants with congenital CMV infection and nephrotic syndrome, one of whom one received anti-CMV therapy while the other did not, and both of them experienced proteinuria remission.…”

Traditional Chinese Medicine in Treating Primary Podocytosis: From Fundamental Science to Clinical Research

“…CMV infection is characterized by focal segmental mesangial hyperplasia with sclerosis, disappearance of foot processes, and membranous nephropathy. Thrombotic microangiopathy is the main pathological change ( Jacob et al, 2020 ). Epstein–Barr virus (EBV) infection is mainly characterized by membranous nephropathy and crescentic glomerulonephritis, and dengue virus infection is mainly characterized by FSGS ( Araújo et al, 2018 ).…”