Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Abstract

Background/Aim: Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. Methods: A total of 168 patients with IgAN were followed up for 6–17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 µM (1.4 mg/dl) in men or 105 µM (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. Results: During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria ≧1 g/24 h at the time of renal biopsy, proteinuria ≧1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. Conclusions: Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (≧1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.

Association of Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and IgA Nephropathy: A Meta-Analysis

“…Therefore, 6 studies without a second PCR to confirm the DD genotype were also excluded [30,31,32,33,34,35]. Furthermore, 1 study was excluded to avoid inclusion of duplicated data as the same patients and controls seemed to be reported in both studies [16, 36]. Finally, 11 studies with 1,339 IgAN patients and 1,881 controls were used in our meta-analysis, and these studies encompassed 6 Caucasian and 4 Asian subject collections as summarized in table 1[11,12,13,14,15,16,17,18,19,20,21].…”

Association of angiotensin-converting enzyme polymorphisms with systemic lupus erythematosus and nephritis: analysis of 644 SLE families

“…Studies of IgA nephropathy, mixed glomerular disease and diabetic nephropathy suggest that ACE polymorphisms are more consistently associated with the progression of renal disease. [22][23][24] Indeed, a previous study of LN among Chinese patients demonstrated association of an Alu I/D genotype with progressive renal disease. 21 Previous studies of ACE polymorphisms in renal and cardiovascular disease demonstrate ethnic heterogeneity with stronger associations in non-Caucasian populations similar to those observed in the current study.…”

Renin-Angiotensin System Polymorphisms: A Risk Factor for Progression to End-Stage Renal Disease in Vesicoureteral Reflux Patients

“…[3] Several studies about the ACE I/D gene polymorphisms in VUR patients have revealed that the D allele might be a risk factor for renal parenchymal damage in children. [7][8][9] Also, the DD genotype has been reported to be associated with reduced renal function in patients with chronic renal diseases like Ig A nephropathy, [10][11][12] focal segmental glomerulosclerosis, [13,14] diabetic nephropathy, [15,16] polycystic kidney disease, [17] and tubulointerstitial nephritis. [18] Because tubulointerstitial damage is also common in VUR, the ACE polymorphism is of interest in this patient group, as it may give clues about the progression of the renal scarring.…”