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

Abstract

Aim. Renin-angiotensin system (RAS) gene mutations have been implicated as a risk factor for the presence and progression of renal disease in vesicoureteral reflux (VUR). However, the results are contradictory, and the effects of RAS polymorphisms in VUR patients with end-stage renal disease (ESRD) have not been defined yet. This study was designed to evaluate the angiotensin-converting enzyme insertion/deletion (ACE-I/D), angiotensinogen (AGT) M235T, and angiotensin II receptor type 1 (ATR1) A1166C and type 2 (ATR2) C3123A gene polymorphisms as risk factors for progression to ESRD in patients with VUR. Methods. ACE-I/D, AGT-M235T, ATR1-A1166C, and ATR2-C3123A were identified in 161 ESRD patients (52 female, 109 male; 77 renal transplant, 84 dialysis; age: 34.4 ± 11.2 years). VUR was the ESRD etiology in 40 patients. Genetic polymorphisms of the ACE gene I/D, AGT gene M235T, ATR1 gene A1166C, and ATR2 gene C3123A were identified in all of the patients. Results. We detected no linkage between genetic polymorphisms of ATR1-, ATR2-, AGT-, and VUR-related ESRD. When ACE gene was considered, VUR(+) patients had 63.6% DD, 36.4% ID, and no II alleles, whereas VUR(−) patients had 48.6% DD, 43.2% ID, and 8.1% II alleles. Conclusion. A striking feature of VUR-related ESRD patients was the absence of II alleles, so the DD genotype may be accepted as a genetic susceptibility factor for progression to ESRD in VUR patients.

Meta‐analysis of the relationship between ACE I/D gene polymorphism and end‐stage renal disease in patients with diabetic nephropathy

“…also performed a study in a Chinese population and reported that the DD genotype might predispose the individual to increased risk of progression to ESRD in IgA nephropathy patients. Akman et al 48 . performed an investigation on Turkish population and reported that the DD genotype was a genetic susceptibility factor for progression to ESRD in vesicoureteral reflux patients.…”

Genetic polymorphism of ACE and the angiotensin II type1 receptor genes in children with chronic kidney disease

“…The I/D polymorphism of the ACE gene and plasma concentration were studied as a cluster of cardiovascular risk factors that could contribute to excess metabolic cardiovascular and renal risks in MHD patients compared with patients undergoing CT. Several reports linked this polymorphism to the development and progression of chronic renal diseases of different etiologies [30-33]. …”

Association of TGF-β1 and TNF-α genes polymorphisms with the kidney scars forming risk in children with vesicoureteral reflux

“…Children who have had an infection of kidney parenchyma have a risk of persistent kidney damage which may result in kidney scarring, hypertension, recurrent urinary tract infections, reflux nephropathy, complications in later pregnancies or, in the worst case, renal insufficiency (RUSHTON, 1997;AKMAN et al, 2009). The presence of vesicoureteral reflux (VUR) is considered as a risk factor for a parenchymal kidney infection and subsequent scarring (NAKAI et al, 2003;MOHANAN et al, 2008).…”

“…Due to dysfunction of the ventricular mechanism of the vesicoureteral compound, manifested by the return of urine from the urinary bladder to the ureter, VUR is the most common anomaly of the urinary tract in children. The ureterovesical junction normally functions as a one-way folding valve which slowly collapses during the filling phase, preventing the retractable return of urine into the ureter and kidney (AKMAN et al, 2009;PURI et al, 2017).…”