HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: CJN.03910808v1 4/6/1065    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Caridi, G. Articles by Ghiggeri, G. M. PubMed PubMed Citation Articles by Caridi, G. Articles by Ghiggeri, G. M.

Clinical Features and Long-Term Outcome of Nephrotic Syndrome Associated with Heterozygous NPHS1 and NPHS2 Mutations

Gianluca Caridi^*, Maddalena Gigante, Pietro Ravani, Antonella Trivelli^*, Giancarlo Barbano^*, Francesco Scolari, Monica Dagnino^*, Luisa Murer^||, Corrado Murtas^¶, Alberto Edefonti^**, Landino Allegri^¶, Alessandro Amore, Rosanna Coppo, Francesco Emma, Tommaso De Palo, Rosa Penza^||||, Loreto Gesualdo, and Gian Marco Ghiggeri^*

^* Division of Nephrology and Laboratory on Pathophysiology of Uremia Istituto Giannina Gaslini, Genova, Department of Biomedical Science, University of Foggia, Foggia, Division of Nephrology, Spedali Civili di Brescia, Brescia, ^|| Department of Pediatrics, University of Padova, Padova, ^¶ Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Parma, ^** Division of Nephrology, Ospedale Maggiore, Milano, Division of Nephrology, Ospedale Regina Margherita, Torino, Division of Nephrology, Ospedale Bambin Gesù, Roma, and Division of Nephrology, Giovanni XXIII Hospital, and ^|||| Department of BioMedicine of Developing Age, University of Bari, Italy; and Departments of Medicine and Community Health Sciences, Faculty of Medicine, University of Calgary, Canada

Correspondence: Dr. Gian Marco Ghiggeri, Laboratorio di Fisiopatologia dell'Uremia, Istituto G. Gaslini, 16148 Genova, Italy. Phone: +39-010-380742; Fax: +39-010-395214; E-mail: labnefro{at}ospedale-gaslini.ge.it

Background and objectives: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS.

Design, setting, participants, & measurements: We reviewed the clinical features of 40 patients with NS associated with heterozygous mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33). Long-term renal survival probabilities were compared with those of a concurrent cohort with idiopathic NS.

Results: Patients with a single mutation in NPHS1 received a diagnosis before those with potentially nongenetic NS and had a good response to therapies. Renal function was normal in all cases. For NPHS2, six patients had single heterozygous mutations, six had a p.P20L variant, and 21 had a p.R229Q variant. Age at diagnosis and the response to drugs were comparable in all NS subgroups. Overall, they had similar renal survival probabilities as non-NPHS1/NPHS2 cases (log-rank ² 0.84, P = 0.656) that decreased in presence of resistance to therapy (P < 0.001) and in cases with renal lesions of glomerulosclerosis and IgM deposition (P < 0.001). Cox regression confirmed that the only significant predictor of dialysis was resistance to therapy.

Conclusions: Our data indicate that single mutation or variant in NPHS1 and NPHS2 does not modify the outcome of primary NS. These patients should be treated following consolidated schemes and have good chances for a good long-term outcome.