TY - JOUR
T1 - Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations
AU - Caridi, Gianluca
AU - Gigante, Maddalena
AU - Ravani, Pietro
AU - Trivelli, Antonella
AU - Barbano, Giancarlo
AU - Scolari, Francesco
AU - Dagnino, Monica
AU - Murer, Luisa
AU - Murtas, Corrado
AU - Edefonti, Alberto
AU - Allegri, Landino
AU - Amore, Alessandro
AU - Coppo, Rosanna
AU - Emma, Francesco
AU - De Palo, Tommaso
AU - Penza, Rosa
AU - Gesualdo, Loreto
AU - Ghiggeri, Gian Marco
PY - 2009
Y1 - 2009
N2 - 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 x2 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.
AB - 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 x2 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.
UR - http://www.scopus.com/inward/record.url?scp=69249231160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69249231160&partnerID=8YFLogxK
U2 - 10.2215/CJN.03910808
DO - 10.2215/CJN.03910808
M3 - Article
C2 - 19406966
AN - SCOPUS:69249231160
VL - 4
SP - 1065
EP - 1072
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
SN - 1555-9041
IS - 6
ER -