Megumi Teranishi

Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure.

Objectives Human adrenomedullin precursor is converted to glycine-extended adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin. Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m). The aim of the present study was to investigate (i) whether sex or age influences plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the ratio of AM-m and AM-total (T) in plasma of various veins and aorta. Methods We measured plasma levels and urinary excretions of AM-m, AM-Gly and AM-T (AM-m + AM-Gly) by recently developed immunoradiometric assay in normal subjects (n = 81), HT (n = 28) and CRF (n = 30). We also determined the molecular forms of plasma adrenomedullin taken from various sites during angiography in patients with suspected renovascular hypertension (n = 9). Results There were no differences in plasma and urinary excretions of two molecular forms of adrenomedullin among sexes or ages in normal subjects. There was no daytime variation of plasma two molecular forms of adrenomedullin in normal subjects. Plasma AM-m, AM-Gly and AM-T levels were increased in patients with HT and CRF compared with normal subjects, whereas urinary AM-m, AM-Gly and AM-T excretions were decreased in patients with HT and CRF compared with normal subjects. Urinary AM-m : AM-T ratios were significantly higher than plasma AM-m : AM-T ratios. Plasma AM-m and AM-T levels taken from various veins were similar, and they were significantly higher than those of aorta, although there were no differences in plasma AM-Gly levels between aorta and veins. Conclusions These results suggest that in normal subjects, and individuals with HT and CRF: (i) plasma and urinary excretions of AM-m and AM-Gly are not affected by age or sex; (ii) AM-m in parallel with AM-Gly is increased; (iii) urine contains a higher percentage of active adrenomedullin than plasma; and (iv) plasma AM-m may be partly metabolized in the lung.

Urinary excretion of liver fatty acid-binding protein in health-check participants

BackgroundMessenger RNA of liver fatty acid-binding protein (L-FABP) is expressed in proximal tubules of the kidney, and a certain amount is excreted into urine. We analyzed factors relating to the urinary L-FABP excretion in health-check participants.MethodsWe measured L-FABP in the first morning urine by ELISA in 715 men and 193 women 30–79 years of age who entered a 2-day hospitalized health checkup program. In addition to the routine physical examination and laboratory tests, plasma high-sensitivity C-reactive protein (HSCRP) was assayed.ResultsIn 150 healthy subjects, urinary L-FABP averaged 3.6 ± 0.2 µg/g creatinine, whereas the values were significantly increased in patients with hypertension (5.2 ± 0.4, P = 0.010), diabetes mellitus (5.5 ± 0.5, P < 0.001), and chronic hepatitis (5.8 ± 1.0, P = 0.022). Urinary L-FABP excretion was significantly greater in women than in men when the value was related to creatinine. In regression analysis in men, urinary L-FABP was positively correlated with fasting plasma glucose (r = 0.103, P = 0.033) and plasma HSCRP (r = 0.135, P = 0.006).ConclusionsIt is suggested that renal production and urinary excretion of L-FABP are increased in situations in which arteriosclerosis is promoted, such as hypertension, diabetes mellitus, and cardiovascular inflammation.

Insertion/deletion angiotensin converting enzyme gene polymorphism affects the microvascular structure of the kidney in patients with nondiabetic renal disease.

OBJECTIVE It has been reported that the deletion allele of the insertion/deletion polymorphism of the angiotensin I converting enzyme gene is associated with increased cardiovascular risk and progressive renal disease, including immunoglobulin A nephropathy. We therefore investigated the relationship between angiotensin converting enzyme polymorphism and intrarenal microvascular structure in 56 patients with nondiabetic renal disease. METHODS AND RESULTS We determined various cardiovascular hormones of the renin-angiotensin system and angiotensin converting enzyme gene polymorphism in 56 patients with nondiabetic renal diseases who underwent a renal biopsy. The patients were divided into three groups by angiotensin converting enzyme genotype (insertion/insertion, n = 21; insertion/deletion, n = 23; deletion/deletion, n = 12) using polymerase chain reaction methods. The angiotensin converting enzyme insertion/ deletion and deletion/deletion genotypes were associated with a significantly higher interlobular artery wall : lumen ratio than the insertion/insertion genotype (insertion/insertion 0.27 +/- 0.01, insertion/deletion 0.32 +/- 0.01, deletion/deletion 0.33 +/- 0.02; P < 0.05). Afferent arteriolar and tubulo-interstitial injury scores were similar among the three genotypes. Although serum angiotensin converting enzyme activity was higher in the deletion/deletion than in the other two genotypes (insertion/insertion 9.7 +/- 0.7, insertion/deletion 10.7 +/- 0.9, deletion/deletion 14.0 +/- 2.4 IU/I; P < 0.05), other factors of the renin-angiotensin system, including blood pressure and serum creatinine levels, were not different among the three groups. CONCLUSIONS The angiotensin converting enzyme deletion/deletion genotype may be considered a risk factor for the development of microvascular wall thickening in nondiabetic renal diseases.