Cardiac malformations associated with the congenital nephrotic syndrome

Grech, Victor; Chan, Man Khun; Vella, Cecil; Montalto, Simon Attard; Rees, Philip; Trompeter, Richard S.

doi:10.1007/s004670000401

Cited by 15 publications

(11 citation statements)

References 12 publications

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“…The heart defects that were detected in our patients are similar to those reported in other children with familial SRNS and CNF, including primarily cardiac hypertrophy, pulmonary stenosis, and discrete subaortic stenosis (8,9,15). That a number of cardiac anomalies are shared by patients with CNF favors the mechanism of direct effect of nephrin and/or podocin instead of an indirect effect of a closely linked mutated gene.…”

Section: Discussionsupporting

confidence: 81%

“…ular bases of the various recessive forms of SRNS, the exact cause of their renal disease remained unknown. Grech et al (9) described four children who were from Malta and had CNF and cardiac malformations: Three had valvular pulmonary stenosis, and one had discrete subaortic stenosis. The diagnosis of CNF was based on histologic findings of kidney biopsies.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few case reports described an association between SRNS and cardiac defects (8,9). The aim of this study was to review systematically the cardiac status of these SRNS patients at the time of diagnosis and during the course of the disease.…”

mentioning

confidence: 99%

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The Heart of Children with Steroid-Resistant Nephrotic Syndrome

Frishberg

Feinstein²,

Rinat³

et al. 2006

Journal of the American Society of Nephrology

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Mutations in the gene NPHS2 encoding podocin are responsible for a recessive form of steroid-resistant nephrotic syndrome (SRNS). The common phenotype is of massive proteinuria in early childhood that tends to progress to end-stage renal failure. Extrarenal manifestations have not been described. Twenty-two children with SRNS from six unrelated Arab families were found to be homozygous for the R138X mutation in NPHS2. Eighteen patients underwent cardiac evaluation at diagnosis of SRNS while they had normal BP and preserved renal function. Cardiac anomalies were detected in 16 (89%) children: Left ventricular hypertrophy in eight, pulmonary stenosis in six, discrete subaortic stenosis in two, and Ebstein anomaly and ventricular septal defect in one each. The remaining four affected individuals were assessed only once they had end-stage renal failure. They had severe left ventricular hypertrophy and experienced repeated episodes of heart failure. Two control groups were equally evaluated. The first consisted of 37 siblings without nephrotic syndrome, of whom only one carrier had a cardiac defect (P < 0.001). None of the second group, which included 22 children with persistent nephrotic syndrome as a result of other causes, had a cardiac anomaly (P < 0.001). Cardiac disorders in homozygotes for mutations in NPHS2 cannot be attributed to an association by chance or to a state of persistent nephrotic syndrome. Because human podocin mRNA is expressed in fetal heart, it is speculated that it may have a role in normal cardiac development. Cardiac evaluation is recommended at the time of diagnosis of SRNS due to mutations in podocin.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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The Heart of Children with Steroid-Resistant Nephrotic Syndrome

Frishberg

Feinstein²,

Rinat³

et al. 2006

Journal of the American Society of Nephrology

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“…Esant baltymo nefrino trūkumui ar defektui, gali iš-sivystyti širdies ar kraujagyslių sistemos ydos. SNS sergantiems vaikams gali būti aptinkamos būdingos širdies ydosširdies ar dešinio skilvelio hipertrofija, subaortinė vožtuvo sklerozė, plaučių arterijos vožtuvo sklerozė [12,13].…”

Section: Klinikiniai Požymiaiunclassified

Suomiško tipo įgimtas nefrozinis sindromas: Literatūros apžvalga ir klinikinis atvejis

Sakalytė

Gurevičienė

Jankauskienė

2015

Medicinos Teorija Ir Praktika

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SANTRAUKAReikšminiai žodžiai: įgimtas nefrozinis sindromas, suomiško tipo nefrozinis sindromas, steroidams atsparus nefrozinis sindromas, inksto transplantacija. Nefrozinis sindromas -reta būklė, kuriai yra būdinga tinimai, proteinurija, hipoalbuminemija ir hiperlipidemija. Du treč-dalius įgimto nefrozinio sindromo atvejų lemia genetiniai sutrikimai. Suomiško tipo nefrozinis sindromas -autosominiu recesyviniu būdu paveldima liga. Šį sindromą lemia įgimti glomerulų filtracinio barjero defektai, kurie išsivysto dėl įvai-rių mutacijų, dažniausiai -NPHS1, rečiau -NPHS2, PLCE1, WT1 ir kt. genuose. NPHS1 geno mutacijos Fin-major (nt121delCT) ir Fin-minor (R1109X) yra susijusios su ankstyva manifestacija ir sunkia ligos eiga. Dauguma šia liga sergančių naujagimių gimsta neišnešioti, mažo svorio, jiems būdinga padidėjusi placenta, įvairios širdies ydos (širdies ar dešinio skilvelio hipertrofija, subaortinė vožtuvo sklerozė, plaučių arterijos vožtuvo sklerozė). Pirmaisiais trimis gyvenimo mėnesiais jiems pasireiškia proteinurija, hipoalbuminemija, hiperlipidemija ir tinimai. Suomiško tipo nefrozinis sindromas gali komplikuotis infekcinėmis ligomis, tromboembolija, hipotiroze, vitamino D trūkumu, anemija. Dėl didelio baltymų praradimo per inkstus pacientams reikia dažnų ar net kasdienių albumino infuzijų. Suomiško tipo nefrozinis sindromas yra atsparus gydymui gliukokortikoidais ir kitais imunosupresantais. Esant nedidelei proteinurijai, galimas konservatyvus gydymas kaptopriliu ir indometacinu. Efektyviausias gydymas -inksto transplantacija. Pacientui atliekama bilateralinė nefrektomija ir vaikas yra dializuojamas tol, kol pagerėja jo būklė ir yra pasiekiama inksto transplantacijai tinkamas 7-9 kg svoris. Šiame straipsnyje pateikiame įdomią 1 m. 7 mėn. mergaitės klinikinio atvejo analizę ir suomiško tipo įgimto nefrozinio sindromo etiologijos, epidemiologijos, klinikinių simptomų, naujausių diagnostikos ir gydymo rekomendacijų apžvalgą.

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“…Overall, cardiac anomalies were detected in 18 out of 20 individuals (89%) and it was speculated, on this basis, that the cardiac phenotype resulted from NPHS2 mutation 'per se'. The association of cardiac malformation with congenital nephrotic syndrome of the Finnish type is not new and the presence of pulmonary stenosis has been reported in a significant portion of these patients [7,8], who notably carry a mutation in NPHS1, the gene coding for nephrin that interacts with podocin in the slit diaphragm. Several observations are, however, against a true association of the cardiac defect with NPHS1 and/or NPHS2 mutations, rather suggesting a casual link: (i) there is a great consanguinity in the Arab pedigrees described by Frishberg, suggesting co-inheritance of two separate genetic defects; (ii) podocin, nephrin and related mRNAs are not expressed by adult heart and are only minimally detectable in fetal heart [1]; (iii) Nphs2 À/À null mice do not develop clinically relevant cardiac anomalies [9], (iv) the four patients of the Arab cohorts who underwent renal transplant recovered normal heart anatomy and function [6].…”

Section: Lack Of Cardiac Anomalies In Children With Nphs2 Mutationsmentioning

confidence: 99%

Lack of cardiac anomalies in children with NPHS2 mutations

Caridi

Dagnino

Carrea

et al. 2007

Nephrology Dialysis Transplantation

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A novel renal perspective of preeclampsia: a look from the podocyte Sir, Preeclampsia (PE) is the most severe hypertensive complication of pregnancy. Onset of proteinuria is the main criterion for diagnosis of PE. Examination of renal biopsies of women with PE shows a pathognomonic lesion known as glomerular endotheliosis (GEN); nonetheless, GEN, from a low to a severe degree, has also been observed in women with gestational hypertension without proteinuria and in healthy pregnant women. Hence, alterations of renal function in women with PE can be attributed to a component of the glomerular filtration barrier (GFB) different from the glomerular endothelium. We propose that proteinuria in women with PE is due to direct injury of podocytes.The GFB possesses three components: the glomerular endothelium, the glomerular basement membrane and epithelial cells known as podocytes. Podocytes assemble forming the slit diaphragm (SD). The SD is located between the foot processes of the podocytes and is composed of a protein complex including Nephrin, NEPH1, NEPH2, FAT1, P-cadherin, Podocin and CD2AP. These proteins interact with each other by way of the foot processes of other podocytes, forming a critical pathway of the GFB. Hence, down-regulation of one of these proteins could be involved in the appearance and development of proteinuria in women with PE. The function of the podocyte and the SD depends on the physiological concentrations of circulating factors, such as vascular endothelial growth factor (VEGF) and its antagonist, the soluble receptor fms-like tyrosine kinase 1 (sFlt-1).Based on findings stating that, (i) GEN is present in women with PE and also in pregnant women without proteinuria, [1] (ii) physiological concentrations of VEGF are important for podocyte homeostasis and survival, [2] (iii) VEGF is important in maintaining of the SD by regulating nephrin expression, [3] (iv) sFlt-1 is a circulating antiangiogenic factor that antagonizes VEGF by binding to it and inactivating it, therefore inhibiting the action of VEGF on the SD, (v) there is an elevated concentration of sFlt-1 in the serum of women with PE as opposed to normotensive pregnant women, [4] (vi) elevated concentrations of sFlt-1 down-regulate the expression of proteins of the SD such as nephrin, [3] and (vii) down-regulation of nephrin expression leads to proteinuria, [5] we propose that proteinuria in patients with PE is mediated not only by endothelium alterations described classically, but also by disturbances of podocyte biology including impaired survival, enhanced apoptosis and down-regulation of nephrin and/or other key proteins of the SD.Conflict of interest statement. None declared.

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Cardiac malformations associated with the congenital nephrotic syndrome

Cited by 15 publications

References 12 publications

The Heart of Children with Steroid-Resistant Nephrotic Syndrome

The Heart of Children with Steroid-Resistant Nephrotic Syndrome

Suomiško tipo įgimtas nefrozinis sindromas: Literatūros apžvalga ir klinikinis atvejis

Lack of cardiac anomalies in children with NPHS2 mutations

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