ASN95 Hot Topic -- ACE Polymorphism and Progression of Renal Disease

The renin-angiotensin system has a pathogenetic role in the progression of CRF. Recent molecular studies have indicated that the ACE gene has a polymorphic insertion/deletion locus with 3 phenotypes (II/ID/DD). The DD phenotype is associated with higher plasma ACE levels and may be indicative of a poorer renal prognosis. A number of centers reported on the predictive value of this phenotype in various renal diseases. Numbers in parentheses indicate abstract and page number in JASN Sept issue.

In a case-control study (1208/721), renal allograft recipients were found to have a higher prevalence of the DD phenotype as compared to healthy donors (41% vs. 25%, p < 0.05), suggesting that pts with DD are at higher risk of developing ESRD than the general population. In diabetic disease, there is some controversy. In 35 pts with IDDM Rxd with ACE inhibitors, DD phenotype along with glyHb and albuminuria were independent risk factors for progression (2250/450). These findings have not been confirmed by all groups (441/457). Similarly, although the DD phenotype was reported to predict the development of nephropathy in IDDM (442/1036), in a study of 257 pts with IDDM from the Netherlands (2252/1037), this phenotype was not predictive of the presence of renal disease. It is possible that DD is not a risk factor for the development of disease but once pts have the disease increases the likelihood of progression. Indeed, Yoshida et al (2253/409) reported that all pts with diabetes and overt proteinuria and the DD phenotype had progression. Increased rate of progression in patients with the DD phenotype and non-diabetic renal disease also appears to be present (2248/390; 2247/407).

If the predictive value of the DD phenotype is confirmed by further data, it is possible that patients who are at higher risk for progression to ESRD can be identified by genetic testing. This has implications for both clinical practice and the design of clinical studies of progression. (David J. Leehey)

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