The Role of Genetic Polymorphisms of Angiotensin-Converting Enzyme in the Progression of Renal Diseases

The renin-angiotensin system is likely to be important in the progression of renal diseases because of its effect on tissue hemodynamics and glomerular cell function. Recent evidence from small studies has suggested a possible role for the genetic determinants of angiotensin converting enzyme activity in the rate of progression of renal failure. We studied the effect of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene on the rate of renal function deterioration in 822 patients with a variety of renal diseases. We found that the slope of the reciprocal serum creatinine–versus-time plot was steeper in patients homozygous for the deletion allele ( DD ) compared with those homozygous for the insertion allele ( II ) ( P =.015). When patients with similar renal function at presentation (creatinine <200 μmol/L) were compared, II homozygotes had significantly improved renal survival ( P =.039). Separate analyses of patients with glomerular diseases and tubulointerstitial diseases demonstrated an effect of this genotype in glomerular diseases only. These data provide further evidence of the possible role of the angiotensin-converting enzyme gene in the rate of progression of renal failure, although further studies are required to evaluate the role of this and other proposed candidate genes in renal diseases.