Takashi Inenaga

Sodium sensitivity and cardiovascular events in patients with essential hypertension

BACKGROUNDnIn patients with sodium-sensitive hypertension, glomerular pressure is increased and microalbuminuria, a marker of glomerular hypertension, is a predictor of cardiovascular events. Similarly, the lack of a nocturnal decrease in blood pressure in these patients is also associated with an increased risk of cardiovascular events. We hypothesised that sodium sensitivity may be the common factor and carried out a retrospective study of cardiovascular events in patients with essential hypertension who had had sodium sensitivity measured in our clinic.nnnMETHODSnSodium sensitivity was assessed in about 350 patients with essential hypertension during the initial investigation of their disorder. The definition of sodium sensitivity was a 10% or greater difference in blood pressure on low-sodium or high-sodium diets. By alphabetical order, the records of 201 patients were obtained and 156 patients without pre-existing disorders were followed up. The records of patients who had a cardiovascular event or died were reviewed without knowledge of the patients sodium-sensitivity status.nnnFINDINGSn62 patients were deemed sodium sensitive and 94 non-sodium sensitive. Left-ventricular hypertrophy was found more frequently in the sodium-sensitive group than in the non-sodium-sensitive group (38 vs 16%; p < 0.01), whereas significantly fewer patients in this group smoked (23 vs 42%; p < 0.05). There were 17 cardiovascular events in the sodium-sensitive group and 14 in the non-sodium-sensitive group. The rate of total, non-fatal and fatal cardiovascular events, was 2.0 per 100 patient-years in the non-sodium-sensitive group and 4.3 per 100 patient-years in the sodium-sensitive group. Coxs proportional-hazards model identified sodium sensitivity (p < 0.01), mean arterial pressure (p < 0.01), and smoking (p < 0.01) as independent cardiovascular risk factors.nnnINTERPRETATIONnCardiovascular events occurred more frequently in patients with sodium-sensitive hypertension. Sodium sensitivity is an independent cardiovascular risk factor in Japanese patients with essential hypertension.

High Sodium Sensitivity Implicates Nocturnal Hypertension in Essential Hypertension

We investigated the relationship between sodium sensitivity and diurnal variation of blood pressure in patients with essential hypertension. Twenty-eight inpatients with essential hypertension were maintained on high sodium (12 to 15 g NaCl per day) and low sodium (1 to 3 g NaCl per day) diets for 1 week each. Twenty-four-hour blood pressure and urinary sodium excretion were measured at the end of each diet period, and the sodium sensitivity index was calculated as the ratio of the change in mean arterial pressure to the change in urinary sodium excretion rate by sodium restriction. Patients whose average mean arterial pressure was lowered more than 10% by sodium restriction were assigned to the sodium-sensitive group (n = 16); the remaining patients, whose mean arterial pressure was lowered by less than 10%, were assigned to the non-sodium-sensitive group (n = 12). In the non-sodium-sensitive group, mean arterial pressure and heart rate fell during the nighttime, and average values of systolic, diastolic, and mean arterial pressures during the night were significantly lower than those during the day during both low and high sodium diets. On the other hand, in the sodium-sensitive group, there was no nocturnal fall in mean arterial pressure, and none of the systolic, diastolic, and mean arterial pressure values during the nighttime was different from the respective pressure values during the daytime during either sodium diet. The sodium sensitivity index was positively correlated with the fall in mean arterial pressure during the nighttime during a high sodium diet (r = .55, P < .01). These results indicate that in patients with sodium-sensitive essential hypertension, blood pressure fails to fall during the night. High sodium sensitivity may be a marker of greater risk of renal and cardiovascular complications, as has been found in nondippers, patients whose blood pressure fails to fall during the night.

Role of systolic blood pressure in determining prognosis of hemodialyzed patients

The role of blood pressure in determining the prognosis of hemodialyzed patients was examined in 195 patients who were introduced to hemodialysis. The relationship between blood pressure and survival or death was analyzed. In 46 patients who died within 3 years after the introduction of hemodialysis (nonsurvivors), the age was higher (61 +/- 2 years v 50 +/- 1 years), the occurrence of diabetic nephropathy was higher, and the systolic pressure was higher in both the introduction (178 +/- 4 mm Hg v 167 +/- 2 mm Hg) and maintenance (165 +/- 4 mm Hg v 147 +/- 2 mm Hg) phases than in 132 patients who survived more than 3 years (survivors). On the other hand, there were no significant differences in diastolic pressure during either phase between the two groups of patients. When diabetic nephropathy was excluded, only systolic pressure during the maintenance phase was higher in the nonsurvivors than in the survivors. Therefore, based on systolic pressure during the maintenance phase, patients were divided into two groups, the HT group (> or = 160 mm Hg) and the NT group (< 160 mm Hg), and cumulative survival rates were compared. Whether all patients, only those patients with diabetic nephropathy, or only those patients without diabetic nephropathy were examined, the survival rate was higher in the NT group than in the HT group.(ABSTRACT TRUNCATED AT 250 WORDS)

The association between salt sensitivity of blood pressure and some polymorphic factors.

Objective To examine the association in Japanese subjects between the salt sensitivity of blood pressure and polymorphic factors. Design and methods One hundred and four patients with essential hypertension were classified as salt-sensitive or non-salt-sensitive depending on their blood pressure response to salt restriction. An insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene was examined by detecting an alu sequence in intron 16. The ACE genotype was classified as II, ID or DD depending on whether each allele had this sequence. The haptoglobin phenotype was determined by the starch–gel electrophoresis method, and was classified as three phenotypes, 1–1, 2–1 or 2–2 form. Results The response of plasma renin activity to salt restriction was greater in patients with the DD form than in those with other forms, although there were no significant differences in the ratio salt-sensitive: non-salt-sensitive patients among the three ACE genotype groups. However, the ratio was significantly larger in the haptoglobin 2–1 phenotype group than in the 2–2 group. Conclusions The salt sensitivity of blood pressure was associated with the haptoglobin phenotype, but was not associated with the ACE genotype. However, the response of plasma renin activity to salt restriction was different according to the ACE genotype.

High sodium sensitivity and glomerular hypertension/ hyperfiltration in primary aldosteronism

Objective To assess sodium sensitivity and glomerular haemodynamics in patients with primary aldosteronism. Design and methods Two-week studies were performed in six patients with primary aldosteronism whose diagnosis had been confirmed by histology of the removed adrenal adenoma. Patients were fed normal or sodium-restricted diets for 1 week each and renal clearance measured during the normal sodium diet. Pressure-natriuresis relationships were drawn by plotting the urinary sodium excretion on the y-axis as a function of the systemic mean arterial pressure on the x-axis. Results The extrapolated x-intercept of the pressure—natriuresis curve was 118 + 9 mmHg. The sodium sensitivity, which corresponds to the reciprocal of the slope, was augmented to 0.111 ± 0.013mmHg/mmol per day, and the reduction in mean arterial pressure by sodium restriction was 11 ± 2%. As we had reported previously, the difference between the mean arterial pressure (137 ± 5 mmHg) with the normal-sodium diet and the x-intercept was assumed to be the effective filtration pressure across the glomerular capillary walls (18.2 ± 2.0 mmHg). By dividing the glomerular filtration rate (128 ± 10ml/min per 1.73 m2) by the effective filtration pressure, the whole kidney ultrafiltration coefficient in these patients was estimated to be 0.127 ± 0.021 ml/s per mmHg, which was approximately normal. The glomerular capillary pressure was calculated to be 54 ± 2 mmHg. Conclusion Compared with non-sodium-sensitive essential hypertension patients (n=18) whose glomerular filtration rate and capillary hydraulic pressure were 84 ± 3 ml/min per 1.73 m2 and 47 ± 1 mmHg, the sodium sensitivity of blood pressure in patients with primary aldosteronism was augmented, and both glomerular hyper-filtration and glomerular capillary hypertension were observed. We confirmed that the glomerular haemodynamic characteristics in primary aldosteronism are typical of those expected for sodium-sensitive hypertension caused by enhanced tubular sodium reabsorption.

Interaction between hypertension and other cardiovascular risk factors in survival of hemodialyzed patients.

The interaction of hypertension with other cardiovascular risk factors, namely hypercholesterolemia, smoking, and past history of cardiovascular complications, was examined. One hundred and ninety-five hemodialysis patients were followed up for 54.2 +/- 2.3 months, among whom 66 died. In patients with cardiovascular complications, such as ischemic heart disease, cerebrovascular accident, or atherosclerotic obliteration of peripheral arteries, and in patients older than 70 years, blood pressure had no significant effect on the already poor survival. On the other hand, in patients with hypercholesterolemia (> or = 220 mg/dL) and in smokers, elevated systolic blood pressure made the survival significantly worse. These results suggest an interaction between hypertension and other cardiovascular risk factors in hemodialysis patients.

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.

Immunotactoid glomerulopathy: Report of a case

We report a 51-year-old man diagnosed as having immunotactoid glomerulopathy (IT) who achieved partial remission after approximately 1 year of a low-dose prednisolone regimen. On admission, he was noted to show proteinuria, hypoproteinemia, and hypocomplementemia. On electron microscopy of the renal biopsy specimen, the mesangial and subendothelial areas were expanded because of the electron-dense deposits, which were represented by mostly straight and nonbranching hollow microtubule structures. The microtubular width was on average 22.0 nm. Clinical and histological findings did not support the diagnosis of amyloidosis, cryoglobulinemic glomerulonephritis, systemic lupus erythematosus, or paraproteinemias. Under treatment with oral prednisolone, 4 months later, the patients serum albumin level increased from its lowest level of 2.3 to 3.6 g/dL, and CH50 from the lowest level of less than 6.3 to 32.4 U/mL. A 24-hour collection of urine showed that the protein had decreased from its highest level of 3.9 g to 2.0 g. This case suggests the effectiveness of long-term, low-dose prednisolone therapy for IT.

Idiopathic Left Innominate Vein Stenosis Manifested following the Creation of Arteriovenous Fistula in Uremia

A 48-year-old woman on maintenance hemodialysis was admitted with her left upper limb swollen and her left jugular vein dilated following the creation of an arteriovenous fistula on her left arm. The intracorporeal pressure during hemodialysis was found to be high. Venographic investigation showed severe stenosis of her left innominate vein accompanied by rich blood flow of the collaterals. Ligation of her fistula promptly reduced swelling of her left upper limb and dilatation of the left jugular vein. The exact cause of the stenosis could not be determined from venographic or computerized tomography findings. Idiopathic left innominate vein stenosis was diagnosed which we believe is the first case to be reported in a hemodialyzed patient.

Plasma Renin Activity in Hemodialyzed Patients During Long-Term Follow-Up

Plasma renin activity (PRA) and mean arterial pressure (MAP) were determined in 11 patients after the initiation of maintenance hemodialysis for 8 to 10 years. PRA increased significantly from 2.3 +/- 0.5 to 6.5 +/- 1.3 ng/mL/h, whereas MAP was lowered during follow-up, and there was a strong correlation between these two (r = 0.88, P < 0.001). Immediately before initiating hemodialysis, PRA was negatively correlated with the increase in PRA (r = 0.62, P < 0.05) and positively correlated with the reduction in MAP (r = 0.65, P < 0.05). PRA was elevated and MAP was markedly reduced in patients whose PRA was relatively low immediately before initiating hemodialysis, whereas PRA tended to be reduced and MAP was unchanged in patients with higher levels of PRA. These data suggest that renin secretion continues even after disuse atrophy of the kidneys with almost complete deterioration of its excretory function.