Angiotensin-Converting Enzyme Gene Polymorphism in Children with Idiopathic Nephrotic Syndrome

Abstract

Aims: To investigate the genetic polymorphism of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) in children with idiopathic nephrotic syndrome (INS), as well as its relationship with patient’s clinical response to steroid therapy. Methods: Fifty-nine patients with INS were recruited and divided into 2 groups according to their clinical response to steroids: steroid-sensitive (SS) with 19 patients and non-SS with 40 patients, which was further divided into steroid-dependent (SD) and steroid-resistant (SR) groups with 35 and 5 patients, respectively. Seventy-nine children without previous renal diseases and negative proteinuria were enrolled as a control group. The genotypes for ACE I/D polymorphism, including DD, ID, and II, were analyzed. Results: The distribution of ACE DD, ID, and II genotypes in INS patients were 52.5, 10.2 and 37.3%, respectively; the corresponding numbers for the control group were 2.5, 25.3 and 72.2%, respectively. Patients with INS had a significantly higher percentage of DD genotype (p <0.001) than the control group. This higher incidence of the DD genotype was observed in both the SS and non-SS groups. A higher percentage of the DD genotype in the non-SS group and in the SD group as compared to the SS group (both p < 0.05) was also noted. Conclusion: Our data shows that INS is associated with a higher incidence of the DD genotype, especially in non-SS patients. This finding suggests that the DD genotype may be a risk factor for INS and play a role in the clinical response to steroids.

Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism on steroid resistance in Egyptian children with idiopathic nephrotic syndrome

“…15 It is difficult to predict at onset the clinical course in terms of steroid responsiveness or resistance. 3 Oral corticosteroids are the first line treatment for a child with INS. Although most children with INS respond to corticosteroid therapy, one half of them become steroid dependent (SDNS) with a clinical course stretched over many years.…”

“…Proteinuria was considered to be in the nephrotic range 3 Regarding renal function, the patients were classified as having either stable renal function or declining renal function (DRF). DRF was defined as doubling of serum creatinine from the onset of the nephrotic syndrome to the time of the study.…”

“…Steroid sensitive (SS) was defined as remission after a 4-week course of full-dose prednisolone treatment; whereas steroid non-sensitive (non-SS) was further subdivided into steroid resistant: persistence of proteinuria after a 4-week course of full-dose prednisolone treatment 3 and steroid dependent: relapse with switch of steroids to alternate day/tapering regimen or within 2 weeks of steroid withdrawal.…”

“…3 It is, however, difficult to predict the course of the disease in terms of steroid responsiveness or steroid resistance. 4 ACE inhibitors and angiotensin receptor blockers reduce proteinuria in patients with nephrotic syndrome, 5 stressing the role of the RAAS in the pathogenesis of nephritic syndrome.…”

A Brief Overview Of Childhood Nephrotic Syndrome: Review

“…109,110 Başka bir çalışmada, ACE inhibitörü geni DD genotipi (homozigot delesyon) olan hastalarda SBNS ve SDiNS, SDuNS'ye göre daha fazla bulunmuş-tur. 111 Bu çalışma bize, ACE'nin steroide verilen klinik yanıtın regülasyonundaki rolünü göster-mektedir.…”