Glomerulopathy And Antihypertensive Treatment

Glomerulopathy is observed as early as 2 years after onset of diabetes [34] and is associated with the level of nocturnal diastolic blood pressure after 10 years in children and adolelescents in whom persistent microalbuminuria has not developed [35]. Antihypertensive treatment has been shown to have a beneficial effect on the course of nephropathy. Further, several recent data present evidence that administration of this treatment regimen in the stage of microalbuminuria to normotensive patients has protective effect [36].

To investigate the influence of angiotensin converting enzyme inhibitors

(ACEI) or beta-blockers on renal structural changes in Type I diabetes, we studied 13 young normotensive patients with microalbuminuria [37]. Patients were randomised to either an ACE-inhibitor (enalapril 20 mg daily, n=7) or a beta-blocker (metoprolol 100 mg daily, n=6), and renal biopsies were taken before and after 36-48 months' treatment. As a reference group we used 9 patients on conventional insulin treatment and without antihypertensive treatment (AHT) that had renal biopsies previously taken with 26-34 months' intervals [31]. These patients had similar age, duration of diabetes and degree of microalbuminuria as those on AHT. We found that BMT, diabetic glomerulopathy index (DGP, figure 2) [i.e. BMT/10+Vv(mat/glom)%] and interstitial fractional volume increased during follow-up in the reference group only. Microalbuminuria was normalised in both the ACEI-treated and the beta-blocker-treated groups, but not in the reference group. Mean HbA1c during the study period did not differ significantly between groups, whereas mean diastolic blood pressure was significantly lower in the antihypertensive groups than in the reference group. It was also found that mean diastolic blood pressure correlated significantly to the changes in BMT, DGP index and the interstitial expansion.

Fig 2. Glomerulopathy index (BMT/10 + Vv(matrix/glom) %) in baseline (B) and follow-up biopsies (F) in three groups treated with ACEI, beta-blocker or conventional insulin treatment. The increase in the reference group is statistically significant (p=0.007) and this group is significantly different from the two other groups (p=0.02 and 0.03 respectively) [37].

Thus our data suggest that progression of early renal structural changes may be prevented or delayed during a 3 year period, by the use of either ACEI or beta-blocker. It is likely that this effect is due to maintenance of a normal or low blood pressure.

These results are in contrast to the data from the ESPRIT study where neither ACEI (enalapril 10 mg once daily) nor Ca-antagonist (nifedipine 10 mg twice daily) did affect the glomerulopathy changes [38]. It should be kept in mind though, that patients in the ESPRIT study had a longer diabetes duration and were older, but more important, they were in a more advanced stage of diabetic nephropathy and the dosage of enalapril was lower than in those included in our study.

We also studied the association between I/D polymorphism of the ACE-gene and progression of diabetic glomerulopathy in the same groups of patients referred to above, i.e those treated with either ACE-I or betablocker, and those without AHT. To extend the number of subjects another group of 9 patients on insulin pump treatment but without AHT, who likewise had renal biopsies previously performed, were included [31]. We found that eight patients had II-, 19 had ID-, and 3 had DD-genotypes, but only those with ID-or DD-genotypes showed any progression in BMT or DGP-index. Among patients with ID-or DD-genotypes progression of BM thickening and DGP-index was more marked in those without AHT than in those with any AHT. However, presence of the D-allele and not having AHT were both variables with an independent influence on the progression of BM thickening. These data indicate that microalbuminuric type 1 diabetic patients who are carriers of the D-allele do benefit from the use ACEI as well as beta-blockers [39].

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