Plasma renin and prorenin and renin gene variation in patients with insulin-dependent diabetes mellitus and nephropathy

Background, The most striking abnormality in the renin-angiotensin system i n diabetic nephropathy (DN) is increased plasma prorenin. Renin is thought to be low or normal in DN. In spite of altered (pro)renin regulation the re nin gene has not been studied for contribution to the development of DN. Methods, We studied plasma renin, prorenin, and four polymorphic markers of the renin gene in 199 patients with IDDM and DN, and in 192 normoalbuminur ic IDDM controls matched for age, sex, and duration of diabetes. Plasma ren in and total renin were measured by immunoradiometric assays. Genotyping wa s PCR-based. Results. Plasma renin was increased in patients with nephropathy (median (r ange), 26.3 (5.2-243.3) vs 18.3 (4.2-373.5) mu U/ml in the normoalbuminuric group, P < 0.0001). Prorenin levels were elevated out of proportion to ren in levels in nephropathic patients (789 (88-5481)vs 302 (36-2226) mu U/ml, P < 0.0001). Proliferative retinopathy had an additive effect on plasma pro renin, but not on renin. DN was associated with a BglI RFLP in the first in tron of the renin gene (bb-genotype: n = 106 vs 82 in DN and normoalbuminur ic patients respectively, P = 0.037), but not with three other polymorphism s in the renin gene. A trend for association of higher prorenin levels with the DN-associated allele of this renin polymorphism was observed in a subg roup of patients with DN (bb vs Bb+BB, P = 0.07). Conclusions. The results indicate that in DN there is an increase in both r enin and prorenin levels. A renin gene polymorphism may contribute weakly t o DN. Although speculative, one of the renin gene alleles could lead to inc reased renin gene expression, leading to higher renin and prorenin levels. These may play a role in the pathogenesis of DN.