Disease progression, response to ACEI/ATRA therapy and influence of ACE gene in IgA nephritis.
Various studies have shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (ID) polymorphism may play a role in the progression to end stage renal failure (ESRF) in patients with IgA nephritis (IgAN). In this randomized controlled trial, patients were followed up for 5 years to determine their long-term renal outcome to ACEI/ATRA therapy and to ascertain if their ACE gene profile could play a role in determining their response to therapy. Seventy-five patients with IgAN were enlisted. Thirty-seven were on ACEI/ATRA therapy for 62+/-5 months and thirty-eight were untreated and served as controls. All patients had their ACE gene ID polymorphism genotyped. Compared to controls, treated patients had lower serum creatinine (p < 0.001), lower proteinuria (p < 0.002) and fewer numbers progressing to ESRF (p < 0.002). Among patients with genotype II, there were less ESRF in the treatment group when compared to the untreated control group (p < 0.02). The advantage of therapy was not seen in patients with ID or DD genotypes. ACEI/ATRA therapy was found to be effective in retarding disease progression in IgAN with years to ESRF significantly extended in patients at all levels of renal function, including patients whose outcome were ESRF. Genotyping showed better response to therapy only for those with genotype II. The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF.
Woo
Keng Thye
KT
Department of Renal Medicine, Singapore General Hospital, Singapore. woo.keng.thye@sgh.com.sg
Lau
Yeow Kok
YK
Zhao
Yi
Y
Liu
Fang E
FE
Tan
Hwee Boon
HB
Tan
Eng Keng
EK
Stephanie
Fook Chong
FC
Chan
Choong Meng
CM
Wong
Kok Seng
KS
D000293:Adolescent; D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A