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)
Use
back arrow on your browser to go back to HDCN home page (faster) or
click on the arrow.