Analysis of 14 Patients With Congenital Nephrotic Syndrome

Chen, Yan; Zhang, Yanqin; Wang, Fang; Zhang, Hongwen; Zhong, Xing; Hu, Xin; Yao, Yong; Jiang, Yi; Ding, Jie; Hou, Xinlin

doi:10.3389/fped.2019.00341

Cited by 13 publications

(23 citation statements)

References 18 publications

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“…One of these biopsies also demonstrated mesangial sclerosis (#4). This contrasts with the findings in patients with GCV "resistant" (mutation "positive") CNS (#3, 7, and 8) (12,14), where light microscopic findings demonstrate a spectrum of normal-appearing glomeruli (#3a), glomerular sclerosis (#3b and 8) and occasional cellular or fibrocellular crescents, as well as focal mesangial proliferation (#7 and 8).…”

Section: Kidney Biopsy Results In the Literaturecontrasting

confidence: 75%

“…A kidney biopsy was performed 15 days after hospitalization (6 days after initiation of VGC treatment) to differentiate the pathohistological changes underlying the nephrotic presentation (1,2,4,12). The majority of the >100 sampled glomeruli showed mild mesangial hypercellularity with patent capillaries and normal glomerular basement membrane (GBM) contours.…”

Section: Kidney Biopsymentioning

confidence: 99%

“…Our survey identified only three cases with a complete tetrad: one patient with a homozygous NPHS2 pathogenic variant, one patient with reported pathogenic variants in both NPHS1 and COL4A5 (however the number of variants and the phase of the variants in each gene was not detailed), and one with no detectable variants in NPH1, NPH2, and WT1 ( Table 2; patients #3, 7, and 6, respectively) (12,14,31). All three patients were treated with ganciclovir (GCV).…”

Section: Cmv-associated Congenital and Infantile Nephrotic Syndromementioning

confidence: 99%

“…Congenital infections, particularly CMV and Treponema pallidum (syphilis), and occasionally Toxoplasma gondii, and other pathogens, have long been associated with rare instances of CNS (5)(6)(7)(8)(9)(10)(11)(12). Although CMV and cytomegalic inclusions have been demonstrated (predominantly) in renal tubular epithelial cells of patients with various CMV-associated glomerulopathies (7,13), the causative role and the pathomechanism of the virus in cases of glomerulonephritis and nephrotic syndrome are still debated (4,10,14).…”

Section: Introductionmentioning

confidence: 99%

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Case Report: CMV-Associated Congenital Nephrotic Syndrome

et al. 2020

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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.

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Section: Kidney Biopsy Results In the Literaturecontrasting

confidence: 75%

Section: Kidney Biopsymentioning

confidence: 99%

Section: Cmv-associated Congenital and Infantile Nephrotic Syndromementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Case Report: CMV-Associated Congenital Nephrotic Syndrome

et al. 2020

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“…Data on the histopathological findings in the kidney tissues were reported for 67 patients, including fetal autopsies on stillbirths (n = 10) and terminations of pregnancy (n = 39) [30,31,36,44,46,47,49,52], autopsies on infants with cCMV infections that died in the first months of age (ranging from minutes of life to 5 months of age) [32,34,37,38,42,43,45,50], and kidney biopsies (n = 4) in cCMV-infected infants with suspected renal disease [33,35,51]. The main histopathological features that were observed are summarized in Table 2.…”

Section: Kidney Involvement At the Pathologic Levelmentioning

confidence: 99%

Renal Involvement in Congenital Cytomegalovirus Infection: A Systematic Review

Ríos-Barnés¹,

Fortuny

Alarcón

et al. 2021

Microorganisms

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Background: Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients. Objective: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels. Methods: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible. Results: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established. Conclusions: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.

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