Evaluation of intrarenal hemodynamics by Doppler ultrasonography for renoprotective effect of angiotensin receptor blockade.

AIMS: It has been shown that both angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB) have renoprotective effects via mechanisms that are independent of blood pressure reduction. The aim of this study was to evaluate the intrarenal hemodynamic change with ARB by renal Doppler ultrasonography (RDU) and to assess the mechanism of ARB in patients with hypertension. METHODS: Thirty hypertensive patients with renal insufficiency caused by glomerular diseases, diabetes and hypertensive nephrosclerosis were included in this study. RDU was performed before and one week after taking ARB. Resistance index (RI) (peak systolic velocity - end diastolic velocity/peak systolic velocity) in the intrarenal segmental artery were calculated, and the amounts of urinary protein or albumin were determined. RESULTS: We defined patients whose microalbuminuria or proteinuria was reduced by greater than 30% by ARB as responders (n = 22) and defined other patients as non-responders (n = 8). There were no significant differences between the responder and non-responder groups in baseline characteristics. RI was significantly improved by ARB in the responder group, but not in the non-responder group. The reduction of RI after ARB treatment was most prominent in patients with hypertensive nephrosclerosis. CONCLUSIONS: Improvement in intrarenal hemodynamics might play an important role in the mechanisms of the renoprotective effect of ARB in patients with hypertension.

Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus.

AIMS: Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients. METHODS: In 67 patients with non-dialysis CRF as a result of chronic glomerulonephritis (n = 33) or diabetic nephropathy (n = 34), and 134 hypertensive patients with normal renal function, two-dimensional and Doppler echocardiographic examinations were performed, and LV dimension, mass, systolic function, and diastolic function were evaluated. RESULTS: LV mass was increased and LV diastolic dysfunction was advanced in subjects with CRF compared with hypertensive controls. In the comparison of echocardiographic parameters between the two groups of CRF patients, i.e. chronic glomerulonephritis and diabetic nephropathy groups, all indices of LV diastolic function were more deteriorated in the diabetic nephropathy group than in the chronic glomerulonephritis group, although LV structure including hypertrophy and systolic function did not differ between the groups. In a multiple regression analysis, the presence of diabetes (i.e. diabetic nephropathy group) was a significant predictor of LV diastolic dysfunction in CRF subjects, independent of other influencing factors such as age, blood pressure, renal function, anaemia and LV hypertrophy. CONCLUSION: The present findings suggest that LV diastolic dysfunction, independent of LV hypertrophy, is specifically and markedly progressed in patients with CRF as a result of diabetic nephropathy.

Pregnancy outcome in nephrotic syndrome with mixed connective tissue disease.

We describe two pregnancies of a young woman with mixed connective tissue disease. In June 1983, she was diagnosed as having Raynaud's phenomenon, arthralgia, and proteinuria. She then developed nephrotic syndrome. Methylprednisolone was initially prescribed at a large dose of 1 g/day which was slowly tapered to 5 mg/day. The proteinuria disappeared. During both pregnancies (the first beginning in December 1988 and the second in May 1992), the patient was placed on a prednisolone maintenance dose (5 mg/day). Both neonates were born healthy at term with no complications. Continuing prednisolone may be useful in pregnant women, and aggressive treatment to prevent mixed connective tissue disease exacerbation may be appropriate during pregnancy.

Treatment of severe hypothyroidism reduced serum creatinine levels in two chronic renal failure patients.

Short-term hypothyroidism has been associated with a reversible rise in serum creatinine levels in patients with normal renal function. A remarkable decline in serum creatinine levels associated with a treatment of severe and prolonged hypothyroidism has rarely been reported so far. We present here 2 patients with chronic renal failure in whom treatment for hypothyroidism resulted in a significant and sustained reduction of their serum creatinine levels. These cases indicate that because hypothyroidism may aggravate the serum creatinine levels, TSH should be considered in screening procedures of patients with chronic renal failure presenting with recent accelerated aggravation of renal function. Hypothyroidism per se, one of its complications or one of its associated autoimmune diseases might play a role in modifying the underlying renal problem.

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.

Cause of residual hypertension after adrenalectomy in patients with primary aldosteronism.

The cause of residual hypertension after adrenalectomy for primary aldosteronism (PA) is unknown. The purpose of this study is to investigate the characteristic pathological kidney features associated with PA. Between 1977 and 1999 at our hospital, 26 patients with PA caused by a unilateral adrenal cortical adenoma (Conn's syndrome) underwent unilateral adrenalectomy with concurrent open-wedge renal biopsy. Patients were categorized into two groups: (1) those with normotension with diastolic blood pressure less than 90 mm Hg who were not administered antihypertensive drugs, and (2) those with residual hypertension with diastolic blood pressure of 90 mm Hg or greater who were administered medication for 6 months after surgery. Thirteen patients were cured of hypertension postoperatively, and 12 patients were administered antihypertensive medications. Glomerulosclerosis, renal arteriolosclerosis, and preoperative left ventricular mass (LVM) index were worse in the group with residual hypertension than in that with normotension (17.8% +/- 7.8% versus 9.6% +/- 3.8%; P = 0.01; 2.5 +/- 0.5 versus 1.6 +/- 0.4, Bader's grade; P = 0.005; and 165 +/- 31 versus 139 +/- 24 g/m(2); P = 0.02, respectively). Severity of tubulointerstitial injury, preoperative duration of hypertension, preoperative severity of proteinuria, plasma aldosterone level, and serum potassium concentration were not significantly different between the two groups. In conclusion, severity of glomerulosclerosis and arteriolosclerosis and LVM are related to blood pressure after adrenalectomy in patients with PA.

Prediction of coronary artery disease and cardiac events using electrocardiographic changes during hemodialysis.

Hemodialysis (HD) patients have a high rate of cardiac morbidity and mortality. Both symptomatic and silent ischemic heart disease may occur frequently during HD because HD simultaneously reduces coronary artery oxygen delivery while increasing myocardial oxygen demand. The purpose of the present study is to prospectively evaluate the usefulness of a significant ST depression induced by HD for the diagnosis of coronary artery disease (CAD) and as the predictor of subsequent cardiac events in HD patients. Sixty-one patients undergoing chronic HD (50 men, 11 women; mean age, 61 years) admitted for such cardiac symptoms as chest pain (n = 43), arrhythmia (n = 5), or heart failure (n = 13) were studied; 38 patients had CAD by coronary angiography. Electrocardiograms performed during HD showed an additional depression (>/=1.0 mV) of the ST segment in 18 patients (positive-ST group), but not in 43 patients (negative-ST group). The incidence of CAD was significantly greater in the former (100%) than in the latter group (46%). A prospective follow-up was performed for 21 +/- 2 months, and cardiac events occurred in all positive-ST group patients and in 21 negative-ST group patients. Event-free survival was poorer in the positive-ST group (P < 0.0001). A Cox proportional hazards model identified the significant ST depression as an independent risk factor for cardiac morbidity (P < 0.05), but not for all-cause mortality. ST depression during HD is useful to diagnose CAD in symptomatic patients and is considered an important prognosticator of subsequent cardiac events.

Exacerbation of renal failure due to hypothyroidism in a patient with ischemic nephropathy.

A case of acute-on-chronic renal failure in a 70-year-old woman with ischemic nephropathy and primary hypothyroidism is presented. Her renal function became progressively worse as the level of serum creatinine increased from 283 to 628 micromol/l (3.2-7.1 mg/dl) within 8 months. Her thyroid function had been normal before the exacerbation of renal failure, but it was markedly reduced with a marked elevation of serum thyroid-stimulating hormone. Thyroid hormone replacement therapy resulted in rapid improvement of the renal function to 159 micromol/l (1.8 mg/dl) of serum creatinine. The development of primary hypothyroidism seemed to worsen the already impaired renal function in this case. We suggest the assessment of thyroid function in patients with unexplained deterioration of renal failure.

Prevalence of renal artery stenosis in autopsy patients with stroke.

BACKGROUND AND PURPOSE: Atherosclerotic renal artery stenosis commonly exists as one manifestation of more generalized atherosclerosis. It is a progressive but potentially curable disorder. Thus, information on renal artery involvement in atherosclerotic diseases could be important. We investigated the prevalence of renal artery stenosis in autopsied patients with stroke over 40 years of age. METHODS: From 2167 consecutive autopsy patients who died between 1980 and 1997, we studied 346 cases of mean age of 69+/-11 years with clinical evidence of stroke. RESULTS: Atherosclerotic renal artery stenosis (>/=75% luminal area narrowing) was found in 36 patients (10.4%). Patients with renal artery stenosis were older and had worse renal function. Renal artery stenosis was found in 14.7%, 28.6%, and 23.9% of patients with hypertension, renal insufficiency, and aortic aneurysm, respectively. Extracranial carotid artery stenosis (>50% luminal area narrowing) was found in 101 patients (29.2%). Of the 346 stroke patients, 256 had a history of brain infarction. In patients with brain infarction, renal artery stenosis was found in 31 (12.1%) and carotid stenosis was found in 81 (33.6%). Patients with carotid artery stenosis were more likely to have renal artery stenosis than patients without carotid artery stenosis (24.4% versus 5.9%, P<0.0001). Multiple logistic regression analysis identified renal insufficiency, hypertension, female gender, and presence of carotid artery stenosis as independent predictors of renal artery stenosis in patients with brain infarction. CONCLUSIONS: These data reveal that atherosclerotic renal artery stenosis is common in patients with stroke, especially in those with brain infarction.

Role of insulin resistance in the genesis of sodium sensitivity in essential hypertension.

We recently showed that cardiovascular morbidity was higher in sodium sensitive type of essential hypertension than in the non-sodium sensitive type. It was examined whether sodium sensitivity was associated with insulin resistance, an important atherosclerotic cardiovascular risk factor in essential hypertension. Fifty-three patients with essential hypertension, who had normal (n = 12) and impaired (n = 41) glucose tolerance, were placed on high (12-15 g NaCl/day) and low (1-3 g) sodium diets for 1 week each to determine sodium sensitivity. Fasting plasma glucose and insulin concentrations were measured on a regular sodium diet. The homeostasis model assessment insulin resistance index (fasting glucose [mmol/L] x fasting insulin [mU/L]/22.5) was 1.40+/-0.10 and 1.47+/-0.14 in non-sodium sensitive and sodium sensitive groups. The insulin resistance index was positively correlated with the sodium sensitivity index, while was negatively correlated with fractional excretion of sodium (FE(Na)) obtained during a high sodium diet. In addition, the insulin resistance index had a positive relationship with overall creatinine clearance. Sodium sensitivity index was also negatively correlated with FE(Na) obtained during a high sodium diet. These results showed that insulin resistance might participate in the genesis of sodium sensitivity in essential hypertension by enhancing tubular sodium reabsorption, as reflected in decreased FE(Na) and augmented creatinine clearance. Insulin resistance seemed elevated in sodium sensitive state of essential hypertension, leading to future cardiovascular events.

Efficacy of percutaneous transluminal coronary angioplasty for patients on hemodialysis. Comparison with those not on dialysis.

Ischemic heart disease has become more important in regard to mortality in hemodialysis (HD) patients. We examined the therapeutic outcome of initial percutaneous transluminal angioplasty (PTCA) in maintenance HD patients with angina pectoris. They consisted of 8 men and 4 women with a mean age of 56.3 +/- 8.6 years and a mean duration of HD of 4.3 +/- 4.0 years. Thirty-six non-HD patients treated with initial PTCA were matched for age, sex and coronary risk factors, and used as a control. Angiographic lesion success was confirmed by angiography in 21 (84%) of the 25 stenotic sites attempted and clinical success was obtained in 9 (75%) of the 12 HD patients, while there were 40 (78%) lesions successfully removed out of the 51 stenotic sites and there were 26 (72%) clinically successful cases out of the 36 non-HD patients, respectively. Angina recurred in 4 (44%) of 9 HD patients, and in 10 (38%) of 26 non-HD patients after successful PTCA, where the follow-up periods were 23 +/- 20 and 28 +/- 25 months, respectively. There was no significant difference in cumulative lesion survival curve between the two groups. In conclusion, PTCA for chronic HD patients is as effective as that for non-HD patients, at least regarding initial PTCA.

Determinants of circadian blood pressure rhythm in essential hypertension.

It has been postulated that the lack of nocturnal blood pressure fall in patients called nondippers is associated with more serious end organ damages by hypertension than in dippers whose blood pressure falls during the night. Recently, we found that sodium restriction shifted circadian rhythm of blood pressure from that of a nondipper to a dipper in patients with essential hypertension. In the present study, we aimed to clarify these important findings from the different approaches, and examined which factors affected the diurnal rhythm of blood pressure. A total of 70 patients with essential hypertension were maintained on high and low sodium diets for 1 week each. Nocturnal fall in mean arterial pressure was calculated in each patient, and, based on multiple regression analysis, independent factors affecting this nocturnal fall were examined. Thirty-eight patients were classified as non-sodium-sensitive, whereas 32 were considered sodium sensitive, based on a >10% change in 24-h mean arterial pressure by sodium restriction. In all 70 patients, sodium sensitivity of blood pressure, as well as an interaction between sodium sensitivity and sodium restriction, were identified as independent factors affecting the nocturnal fall. In sodium-sensitive types, in addition to sodium restriction, glomerular filtration rate was identified, whereas, in non-sodium sensitive types, there was no significant factor. Based on multiple regression analysis, the present study reached the same important conclusion as our previous findings: namely, that the enhanced sodium sensitivity was an independent determinant for the diminished nocturnal fall in essential hypertension and that sodium restriction could restore the nocturnal decline, especially in patients with enhanced sodium sensitivity whose nocturnal decline was diminished. Reduced renal sodium excretory capability may be one of the mechanisms involved in nondipping.

Cardiovascular complications in patients with primary aldosteronism.

Primary aldosteronism (PA) is widely believed to be a relatively benign form of hypertension associated with a low incidence of vascular complications. However, several recent studies showed that cardiovascular complications were not rare in PA. PA is known as one of the most typical forms of sodium-sensitive hypertension. Recently, we found that the sodium sensitivity of blood pressure was a marker for greater risk for cardiovascular complications, especially stroke, in patients with essential hypertension. Therefore, we investigated cardiovascular complications in 58 patients with PA confirmed to be Conn's adenoma. Cardiovascular complications were found in 34% of 58 patients. Coronary artery disease was found in only one patient (1.7%), as angina pectoris. Stroke was found in nine patients (15.5%), four patients (6.9%) with cerebral infarctions and five patients (8.6%) with cerebral hemorrhages. Proteinuria and renal insufficiency were found in 14 (24.1%) and 4 (6.9%) patients, respectively. The incidence of cerebral infarction and renal insufficiency was greater in men than women. The prevalence of proteinuria was greater in patients with than without stroke (P = 0.03) among those aged older than 40 years. These results indicated that cardiovascular complications, especially stroke and proteinuria, were common in patients with PA, and proteinuria might be an indicator for stroke as target-organ damage.

Circadian rhythm of natriuresis is disturbed in nondipper type of essential hypertension.

We examined the circadian rhythm of urinary sodium excretion and the effects of sodium restriction on rhythm in both dipper and nondipper types of essential hypertension. Patients (n = 26) with essential hypertension were maintained on relatively high- (10 to 12 g/d of sodium chloride) and low-sodium (1 to 3 g/d) diets for 1 week each. On the last day of each diet, 24-hour blood pressures (BPs) were measured every 30 minutes noninvasively with an automatic device, and on the last 3 days, urinary samples were collected for both daytime (7:00 AM to 9:30 PM) and nighttime (9:30 PM to 7:00 AM). Eight patients were classified as dippers based on a more than 10% reduction in mean arterial pressure (MAP) from daytime to nighttime on a high-sodium diet, and 18 patients were classified as nondippers. A nocturnal decrease in urinary sodium excretion rate (U(Na)V) on the high-sodium diet was observed in dippers (from 7.5 +/- 2.1 during the day to 5.3 +/- 2.5 mmol/h at night; P < 0.0001), but not in nondippers (6.7 +/- 2.1 v 7.6 +/- 2.3 mmol/h; not significant). In nondippers, the night-day ratio of sodium excretion was significantly reduced from 1.2 +/- 0.4 to 0.8 +/- 0.3 (P < 0.003) by sodium restriction; at the same time, the night-day ratio of MAP was reduced from 0.98 +/- 0.04 to 0.93 +/- 0.05 (P < 0.05). In dippers, the night-day ratios of MAP and U(Na)V were not affected by sodium restriction, and both ratios remained constant at less than 1. Before sodium restriction, the night-day ratio of sodium excretion correlated with that of MAP (r = 0.78; P < 0.0001), whereas there was no significant correlation (r = -0.05) after sodium restriction. These findings showed that the circadian rhythm of renal sodium excretion differed between the two types of essential hypertension. The enhanced nocturnal natriuresis and diminished nocturnal BP fall on a high-sodium diet, recognized in nondippers, were both normalized by sodium restriction, resulting in circadian rhythms with nocturnal dips in U(Na)V and BP.

Changes in the circadian rhythm of blood pressure in primary aldosteronism in response to dietary sodium restriction and adrenalectomy.

OBJECTIVE: Recently, we found that sodium restriction restored the circadian rhythm of blood pressure from non-dippers to dippers in patients with a sodium-sensitive type of essential hypertension. In the present study, we investigated the effects of sodium restriction on the circadian blood pressure rhythm in patients with primary aldosteronism, a typical sodium-sensitive form of secondary hypertension. DESIGN AND METHODS: We performed 24 h blood pressure monitoring in eight patients with primary aldosteronism due to unilateral adenoma (Conn's syndrome) during normal-sodium (7-12 g/day of NaCl) and low-sodium (1-3 g/day) diets, and after adrenalectomy. RESULTS: Sodium restriction lowered the 24 h mean arterial pressure from 116+/-14 to 109+/-12 mmHg (P< 0.01). During a normal-sodium diet, there was no change in systolic, diastolic and mean arterial pressures during the night-time compared with the daytime. In contrast, during a low-sodium diet, all night-time pressure values were significantly lower than those in the daytime. After adrenalectomy, the night-time pressures in patients on a normal-sodium diet were lower than those of the daytime. The nocturnal mean arterial pressure fall was increased by sodium restriction and adrenalectomy. CONCLUSIONS: These results indicate that the circadian rhythm of blood pressure was disturbed in patients with primary aldosteronism who maintained a relatively high sodium intake. Both adrenalectomy and sodium restriction restored a nocturnal dip in blood pressure in primary aldosteronism. Therefore, sodium restriction affects the circadian blood pressure rhythm in sodium-sensitive types of hypertension, not only in primary hypertension, but also in secondary hypertension.