Plasma prorenin levels may predict persistent microalbuminuria in children with diabetes

Abstract

Diabetic microangiopathy is characterized by increased prorenin concentrations. In the present study, we evaluated plasma prorenin concentrations in a large group of adolescents with onset of diabetes during childhood to determine whether increasing prorenin levels may predict the development of persistent microalbuminuria. Ninety-seven young diabetic patients were studied; they were divided according to the presence of persistent microalbuminuria, at the end of follow-up, into group A and group B (patients who did not develop and who developed persistent microalbuminuria, respectively). One hundred and two healthy subjects, matched for age and sex, were also selected. Patients were followed up for at least 10 years. At the beginning of the study there were no significant differences in prorenin levels between either the two diabetic groups or the healthy controls. During follow-up, an increase in plasma prorenin started at 4 years and became statistically significant (P<0.01) 3 years before the onset of persistent microalbuminuria. No correlation was found between plasma prorenin levels and HbAlc percentages. In conclusion, an increased concentration of prorenin in plasma precedes the elevation of albumin excretion rate (AER) and, therefore, can be useful for identifying patients with onset of diabetes during childhood at risk of developing incipient nephropathy later in life.

Renin, (pro)renin and receptor: an update

“…Moreover, HRP could decrease cardiac and renal fibrosis in stroke-prone SHRs (spontaneously hypertensive rats) [31][32][33] and reduce insulin resistance [34]. The great interest in PRR in diabetic nephropathy and retinopathy is explained by the fact that diabetic patients have low active renin levels, but very high prorenin levels, which are reported to be associated with and even to be predictive of the occurrence of microvascular complications as evidenced in microalbuminuria and retinopathy [35][36][37][38], but, in spite of the low renin levels, RAS blockers have a tissueprotective effect, suggesting local RAS activation. In addition, it has been shown that prorenin synthesis was locally enhanced in the collecting duct of diabetic rats [39], and many studies have also shown an up-regulation of PRR in the kidney of diabetic humans [40] and rats [41,42], so that the combination of increased prorenin and PRR may create a local environment favourable for PRR activation and for AngII generation.…”

Hyperreninemia Characterizing Women with Polycystic Ovary Syndrome Improves after Metformin Therapy

“…Interestingly, high total renin levels have been found in several clinical settings characterized by endothelial dysfunction such as heart failure [34] , preeclampsia [35] , diabetic nephropathy [36][37][38][39] and retinopathy [40][41][42] . Therefore, it is likely that increased total renin levels may also contribute to endothelial dysfunction, a known abnormality in patients with PCOS [43][44][45] .…”

Direct Renin Inhibition with Aliskiren in Hypertension and Target Organ Damage

“…The existence of receptors for renin and prorenin may provide an explanation for the long-standing observation that renin and prorenin levels are markers of microvascular complications in patients with diabetes, particularly those involving the eye (29). Indeed, increases in prorenin are associated with the development of retinopathy (29,30) and may also predict the onset of microalbuminuria in patients with diabetes (31). Although at present there is no clinical evidence that prorenin levels per se represent anything more than a marker, Veniant et al (32) generated a transgenic rat that expresses prorenin in the liver and reported that these animals developed cardiomyocyte hypertrophy and renal lesions, despite normal BP values.…”