angiotensinogen and Glomerulonephritis--Membranous

Immunosuppressive treatment will predispose an idiopathic membranous nephropathy (iMN) patient to opportunistic infections. Disease severity is one of the main concerns for making the treatment decision. Urinary angiotensinogen (UAGT) level has been shown highly correlated with intrarenal renin-angiotensin system (RAS) activity and severity of chronic kidney diseases (CKD). We aimed to test the relationship between the UAGT level and the severity of iMN.. This cross-sectional study included a total of 48 biopsy-proven iMN patients, 46 minimal change disease (MCD) patients, and 44 healthy volunteers. The clinical and laboratory data and urine samples were collected from all subjects before the use of RAS inhibitors. We determined the UAGT levels with a method of enzyme-linked immunosorbent assay.. The UAGT levels were not different between the iMN (277.05 ± 61.25, μg/g.Cr) and MCD patients (244.19 ± 40.24, μg/g.Cr), but both of them were significantly higher than those of healthy controls (6.85 ± 1.10, μg/g.Cr). UAGT levels were correlated negatively with serum albumin (r = - 0.393, p = 0.006) and estimated glomerular filtration rate (eGFR) (r = - 0.352, p = 0.014) and positively with 24-h proteinuria (r = 0.614, p < 0.001) in iMN patients but not in MCD patients. Multivariate linear regression analysis revealed that only proteinuria independently determinate the levels of UAGT (β = 0.649, p < 0.001) in iMN patients.. UAGT levels were correlated negatively with serum albumin and glomerular filtration rate and positively with proteinuria in iMN patients at the onset. This suggests that elevated levels of UAGT are associated with the severity of iMN. The UAGT level may be used as a cofactor for deciding immunosuppressive therapy in iMN patient.

Topics: Adolescent; Adult; Aged; Angiotensinogen; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Middle Aged; Nephrosis, Lipoid; Proteinuria; Serum Albumin; Severity of Illness Index; Young Adult

The purpose of our study was to evaluate the correlation of polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS) genes and the development and prognostic implications for immunoglobulin A nephropathy (IgAN)/membranous nephropathy (MN). A polymerase chain reaction was performed for the AGT, ACE, and eNOS genes, followed by DNA sequencing and statistical analysis. There was a difference in ACE gene type II and type I between the IgAN and MN groups (P < .05) and in eNOS gene TT type and T type between the IgAN and MN groups (P < .05 and P < .01). In the IgAN group, significant differences were observed between ACE gene polymorphism and the age group of 20 years or less, male sex group, with/without hematuria, and high blood urea nitrogen (BUN; P < .05 or P < .01); between AGT gene polymorphism and with/without hematuria, high BUN, and pathologic classification (P < .05 or P < .01); and between eNOS gene polymorphism and high BUN and pathologic classification (P < .05 or P < .01). However, in the MN group, significant differences were observed between ACE gene polymorphism and the degree of proteinuria and high BUN (P < .001 and P < .05), between AGT gene polymorphism and with/without hematuria (P < .05), and between eNOS gene polymorphism and the degree of proteinuria and high BUN (P < .05 and P < .01). The ACE, AGT, and eNOS genes were correlated with the development of renal function failure in IgAN, whereas the ACE and eNOS genes were associated with the degree of proteinuria and the development of renal function failure in MN.

Topics: Adolescent; Adult; Angiotensinogen; Disease Progression; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Humans; Kidney; Male; Middle Aged; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide; Proteinuria

The renin-angiotensin system (RAS) and nitric oxide synthase (NOS) play a key role in the progression of primary glomerulonephritis (GN). Although previous studies have examined genetic risk associated with single gene variations, experiments assessing risk conferred by multiple gene variations are still scanty.. The effect of combination of variant alleles of four genes encoding for three components of the RAS [angiotensin converting enzyme insertion/deletion (ACE I/D), angiotensin II receptor 1 (AT1R 1166A/C), angiotensinogen (AGT M235T)] and for NOS (ecNOS4b/a) on the development and progression of membranous GN (MGN) were evaluated in a longitudinal study comparing 117 patients with serum creatinine (s-Cr) <1.5 mg/dl at renal biopsy and follow-up > or = 5 years (Kaplan-Meier and Cox multivariate analysis). The control group consisted of DNA from 171 organ donors.. We found no relationship between single or combined variations of the four gene polymorphisms and development of MGN. Among single gene variations, there were no independent genetic risk factors for the progression of renal disease, after adjustment for age, sex, hypertension, proteinuria, s-Cr, chronicity and activity index. However, double variation coincidences such as the combination of the allele a of ecNOS4b/a and both the allele D of ACE I/D (chi(2) =4.80, P = 0.028; HR = 1.97, 95% CI 0.98-3.96) and the allele T of AGT (M235T) (chi(2) = 5.09, P = 0.024; HR = 2.84, 95% CI 1.39-5.82) exerted an additional effect that was higher than that of the single gene variations.. This study is the first to demonstrate a role for an interaction between simultaneous variations of genes encoding for NOS and components of RAS in the progression of MGN. Interactions between various polymorphisms may explain conflicting results obtained in previous studies that examined single gene variations, since the effect of a single locus variation may be influenced by the simultaneous presence of other variant alleles in polygenic diseases such as primary GN. However, the small sample sizes and possible multiple interactions limited the interpretation of the current findings, which may represent true biological interaction or simply statistical interactions or spurious results due to the small sample sizes.

Topics: Adult; Aged; Angiotensinogen; Case-Control Studies; Female; Genotype; Glomerulonephritis, Membranous; Humans; Longitudinal Studies; Male; Middle Aged; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1