The abstract, titled “GENOTYPE (A) OF ENOS GENE AND R229Q MUTATION OF NPHS2 APPEARS TO BE ASSOCIATED WITH A WORSE OUTCOME IN PATIENTS WITH IGA NEPHROPATHY,” was presented at the European Renal Association-European Dialysis Association’s annual meeting.
Here’s what it reported:
INTRODUCTION AND AIMS: IgA Nephropathy, the most common glomerulonephritis throughout the world, is characterized by an IgA1 deposit of in the glomerular mesangium and it has a very variable clinical course from asymptomatic microscopic hematuria till ESRD. It can be attributed to genetic modifiers that increase the risk of progression of the disease.
The NO role in glomerular microcirculation and function of mesangial cells may be altered by endothelial NO synthesis gene polymorphism. Several studies have shown the influence of eNOS gene polymorphism on the progression of kidney disease. Podocin, a membrane protein is located exclusively at the podocyte slit diaphragm, part of the glomerular filtration barrier and is encoded by NPHS2 on chromosome 1q25- 31.
The aim of this study is to investigate the NPHS2 R229Q mutation and eNOS gene intron 4a/b polymorphism possible association with clinical presentation and progression of IgA nephropathy in a define geographical region (the island of Crete – 0.6 million population) with the same genetic background.
METHODS: 103 patients with biopsy-proven IgA glomerulonephritis were included in our study and a median follow up period of 5.1±2.8 years. All subjects where genotyped for the intron 4a/b polymorphism and screened by sequencing for NPHS2-R229Q mutation. The end-points were doubling in baseline serum creatinine and/or relapse of proteinuria and/or initiation of dialysis.
RESULTS: At baseline, M/F 68/35, age was 41.5±13.5 years, creatinine 1.21±0.74 mg/dl, proteinuria was 1094±1201 mg/24H, 78% of the patients had a baseline creatinine of ≤ 1.3 mg/dl, 57% had a proteinuria of <1000mg/24H. During follow up time, 12 patients (11%) have doubled serum creatinine and 7 of them (8%) started dialysis in a period of 5.1±4.2 years.
40 (39%) patients presented eNOS intron 4 polymorphism a (6 aa,34 ab) and 63 (64%) polymorphism b. Patients reaching the outcome exhibited higher systolic blood pressure (144±20 vs 130±20 mmHg, p=0.02), diastolic blood pressure (82,1±13 vs 72,3±15mmHg, p=0.028), higher baseline creatinine (2.18±2,7 vs 1.34±0,8 mg/dl, p=0.009) and more extended tubulointertitial fibrosis (21% vs 13% , p=0.1)
15 (14%) patients presented R229Q mutation and it was more common in patients with proteinuria ≥ 500 mg/24H.
Combination of polymorphism a (eNOS) and R229Q (NPHS2) was related to an unfavorable outcome, compared with other combinations (HR 3.9 – 95% Cl 1.63-12.5) to 7.2 (95% Cl 2.3-24.4 ) after adjusting for proteinuria, blood pressure and pathological carateristics.
In a multivariate Cox proportional hazard analysis, the presence of a allele of eNOS gene, showed an 8-fold hazard to reach the outcome (HR=8.09, p=0.04) after adjusting for age, sex, presence of hypertension, proteinuria and ACE inhibitors treatment. ACE inhibitors treatment was associated with a hazard ratio of five times less (HR=0.17, p=0,05) in reaching the outcome.
CONCLUSIONS: In our population, the genotype (a) of eNOS gene and R229Q mutation of NPHS2 appears to be associated with a worse outcome. Their interaction in a patient, is a negative prognostic factor for IgA nephropathy. Additionally, The early detection of (a) allele could indicate those patients at increased risk of renal impairment but more extensive studies need to be done.
D. Xydakis: None.
But according to the notice, the second author on the abstract was unaware of his role in the study:
This paper has been retracted at the request of the authors and in accordance with the COPE guidelines. Following an allegation by one of the authors and a consequent investigation by the NDT team, it has emerged that George N. Goulielmos was not aware of his name being included in the list of authors and did not agree with the general conclusions drawn from the data. As a consequence of this, the poster was withdrawn from the 2014 ERA-EDTA congress and consequently has been retracted from the journal in its online form.
The abstract has yet to be cited, according to Thomson Scientific’s Web of Knowledge.