Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

Factors Associated with Outcomes of Percutaneous Transluminal Renal Angioplasty in Patients with Renal Artery Stenosis: A Retrospective Analysis of 50 Consecutive Cases.

BACKGROUND: The results of recent trials have brought some confusion to the treatment strategy for renal artery stenosis (RAS). To evaluate the applicability of percutaneous transluminal renal angioplasty (PTRA) for RAS, we extracted the factors that may affect the effectiveness of PTRA from cases experienced at a hypertension center. METHODS AND RESULTS: We retrospectively assessed the blood pressure (BP) lowering effects and renoprotective effects in 50 consecutive patients that had hemodynamically significant RAS and had undergone PTRA and stenting during 2001-2005. Subjects were diagnosed with atherosclerotic RAS (42), fibromuscular dysplasia (6), or Takayasu disease (2). After PTRA, BP significantly lowered from 152.3/80.3 mmHg to 132.6/73.2 mmHg (p < 0.05), but the estimated glomerular filtration rate (eGFR) did not change significantly. There were no factors associated with the BP lowering effects of PTRA. The baseline resistive index (RI) was negatively correlated with the change in eGFR (p < 0.05). After correction for age, sex, BMI, and the dose of contrast medium, the association of RI with change in eGFR remained significant. CONCLUSION: In cases with hemodynamically significant RAS, PTRA lowered BP but was not effective in improving renal function. Higher baseline RI may be a factor for predicting poor clinical course of renal function after PTRA.

Association of intima-media thickening of carotid artery with genetic polymorphisms of the regulator of G-protein signaling 2 gene in patients with hypertension and in the general population.

Regulator of G-protein signaling 2 (RGS2) is a key molecule in signal pathways of vasoactive peptides, such as angiotensin II and endothelin 1, and is believed to have an important role in the pathophysiology of atherosclerosis. We have previously reported that common polymorphisms of RGS2 are associated with hypertension in Japanese. In this study, we studied whether the three previously identified common polymorphisms of RGS2 (-638A>G, 1026T>A and 1891-1892delTC) could be implicated in carotid atherosclerosis in Japanese patients with hypertension (459 men and 382 woman) and in a Japanese general population (814 men and 956 woman). We assessed two criteria for carotid atherosclerosis: maximal intima-media thickness (M-IMT) and mean-IMT. When subjects with atherosclerotic lesions were defined as having mean-IMT≥1.0 mm, multivariate logistic regression analysis performed after adjusting for confounding factors showed a significant association of the three common polymorphisms, -638A>G (AA versus AG+GG: odds ratio (OR), 1.55; 95% confidence interval (CI), 1.105-2.185; P=0.0113 only for the general population), 1026T>A (TT versus TA+AA: OR, 1.42; 95% CI, 1.027-1.972; P=0.034 for hypertensive subjects and OR, 1.56; 95% CI, 1.129-2.151; P=0.0071 for the general population), and 1891-1892delTC (II versus ID+DD: OR, 1.44; 95% CI, 1.043-2.008; P=0.028 for hypertensive subjects, OR, 1.32; 95% CI 1.002-1.742; P=0.048 for the total general population and OR 1.59; 95% CI 1.155-2.207; P=0.0047 for the general population), with carotid atherosclerosis. When atherosclerosis was defined as M-IMT 1.0 mm, the values of M-IMT were also significantly different between the three genotypes in the three common polymorphisms. Taken together, these data suggest that genetic polymorphisms in RGS2 are associated with intima-media thickening of carotid artery in humans.

Impact of left ventricular end-diastolic wall stress on plasma B-type natriuretic peptide in heart failure with chronic kidney disease and end-stage renal disease.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) is a diagnostic and prognostic marker in heart failure (HF). Although renal function is reported as an important clinical determinant, precise evaluations of the relationships of renal function with hemodynamic factors in determining BNP have not been performed. Therefore, we evaluated the association of plasma BNP concentrations with LV end-diastolic wall stress (EDWS) in a broad range of HF patients including those with chronic kidney disease (CKD) and end-stage renal disease (ESRD). METHODS: In 156 consecutive HF patients including those with CKD and ESRD, we measured plasma BNP and performed echocardiography and cardiac catheterization. LV EDWS was calculated as a crucial hemodynamic determinant of BNP. RESULTS: Plasma BNP concentrations increased progressively with decreasing renal function across the groups (P < 0.01) and were correlated with LV EDWS (r = 0.47) in the HF patients overall. This relationship was also present when patients were subdivided into systolic and diastolic HF (P < 0.01). In multivariable analysis, higher EDWS was associated with increased BNP concentration independently of renal dysfunction (P < 0.01). Anemia, systolic HF, and decreased BMI also contributed to increased BNP concentrations. CONCLUSIONS: These results suggest that LV EDWS is a strong determinant of BNP even in patients with CKD and ESRD. Anemia, obesity, and HF type (systolic or diastolic) should also be considered in interpreting plasma BNP concentrations in HF patients. These findings may contribute to the clinical management of HF patients, especially those complicated with CKD and ESRD.

Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers.

BACKGROUND: The response of blood pressure (BP) to L-type dihydropyridine calcium-channel blockers (dCCBs) differs among individuals. METHODS AND RESULTS: A pharmacogenomic analysis was undertaken in 161 patients with essential hypertension who were treated with dCCBs to study whether genetic polymorphisms of the calcium channel alpha1C and alpha1D subunit genes, CACNA1C and CACNA1D, are associated with the antihypertensive effects of dCCBs. Responders were defined as those in whom systolic BP (SBP) was lowered by more than 20 mmHg or diastolic BP (DBP) was lowered by more than 10 mmHg after treatment with dCCBs. Eleven sequence-proven polymorphisms of CACNA1C and 5 common polymorphisms of CACNA1D chosen from a public database were subjected to genotypic analysis. The comparison of polymorphism prevalence between responders and nonresponders showed significant differences in CACNA1D rs312481G>A and rs3774426C>T, and in CACNA1C 527974G>A. There were significant differences in SBP or DBP between alleles in these single nucleotide polymorphisms (SNPs). A much more significant reduction in BP was observed for the combined presence of these SNPs. CONCLUSIONS: Three SNPs in CACNA1D or CACNA1C are genetic polymorphisms conferring sensitivity to the antihypertensive effects of L-type dCCBs in patients with hypertension. The BP reduction by L-type dCCBs might be predicted by evaluating these polymorphisms.

Renal artery stenosis and renal parenchymal damage in patients with abdominal aortic aneurysm proven by autopsy.

BACKGROUND: Chronic kidney disease is a major risk factor for patients with cardiovascular diseases (CVD). The aim of this study is to evaluate the relationship between clinical characteristics and renal histology in patients with abdominal aortic aneurysm (AAA). METHODS: We studied 79 cases with AAA autopsied at the National Cardiovascular Center. They were classified into two groups: 14 subjects with renal artery stenosis (RAS) (group A) and 65 subjects without RAS (group B). Proteinuria, elevated serum creatinine and decreased estimated glomerular filtration rate had been recorded. We evaluated renal parenchymal damage using a semiquantitative histological score (score 0-3; normal to severe) for glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar hyalinosis (maximal score = 12). RESULTS: Total histological score was 8.2 +/- 2.4 and significantly higher in the stenosed kidneys of group A than in the non-stenosed kidneys of group B (8.9 +/- 2.6 vs. 8.0 +/- 2.3). The histological score had a significant association with RAS, smoking, kidney function, proteinuria, kidney weight and the presence of other CVD. CONCLUSION: We demonstrated that renal parenchymal damage and deteriorated kidney function are closely associated in the patients with AAA. Treatment of these patients in view of protection of the kidney is thus relevant.

Plasma B-type natriuretic peptide levels reflect the presence and severity of stable coronary artery disease in chronic haemodialysis patients.

BACKGROUND: Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality in haemodialysis (HD) patients. Although the plasma B-type natriuretic peptide (BNP) levels may be a strong marker of long-term mortality in HD patients, what plasma BNP levels reflect is not well known in this setting. Therefore, we examined the relationship between plasma BNP levels and the presence and severity of stable CAD based on coronary angiography (CAG) in chronic HD patients. METHODS: Plasma BNP levels were measured in 179 consecutive HD patients who were referred for CAG due to symptoms or objective signs of stable CAD. Left ventricular end-diastolic wall stress (LV EDWS) was also calculated as a crucial haemodynamic determinant of plasma BNP. RESULTS: Plasma BNP levels were significantly higher in patients with CAD than in those with non-CAD. The area under the receiver operating characteristic curve for BNP to predict CAD was 0.837. Plasma BNP levels increased progressively with the extent of CAD [1-vessel disease (VD), 496 +/- 49 pg/ml; 2-VD, 932 +/- 119 pg/ml; 3-VD, 2073 +/- 317 pg/ml; P < 0.01]. LV EDWS was well correlated with plasma BNP levels (r = 0.61, P < 0.01), and a multivariable regression analysis that took into account EDWS demonstrated a significant association between the extent of CAD and BNP (P < 0.01). CONCLUSIONS: These results suggest that the presence and severity of stable CAD determine plasma BNP levels in chronic HD patients. Plasma BNP levels may be a useful marker in the management of HD patients.

The cutoff value of aldosterone-to-renin ratio for the diagnosis of primary aldosteronism in patients taking antihypertensive medicine.

BACKGROUND: Primary aldosteronism (PA) may account for as much as 6-20% of cases of refractory hypertension referred to hypertension clinics. Because antihypertensive agents affect the physiologic renin-angiotensin-aldosterone system, screening diagnostic tests for PA are generally performed after antihypertensive agents are discontinued. However, such tests can be dangerous for patients with severe hypertension or other cardiovascular complications. However, a reliable cutoff value for the aldosterone-to-renin ratio (ARR) has not been established, especially for Asians, including the Japanese. METHOD: Fifty-five consecutive patients with clinically suspected PA were evaluated from July 10, 2001, to March 1, 2005, at the National Cardiovascular Center in Japan. Every referred patient was screened prospectively for PA with the ARR at the outpatient clinic. The patients tested continued to be treated with a variety of antihypertensive agents. We reviewed the sensitivity, specificity, and accuracy of the ARR without modifying the antihypertensive agents. The diagnosis of PA was established with the results of both abdominal computed tomography and adrenal scintigraphy. RESULTS: Of the 55 patients, 27 were found to have PA, including adrenal adenoma (n = 18) and bilateral adrenal hyperplasia (n = 9). The mean ARR of patients with PA was significantly higher than that of patients without PA. By assuming a cutoff value of the ARR >or= 69 calculated from the receiver operating characteristics curve, the highest sensitivity (81%), specificity (82%), positive-predictive value (81%), and negative-predictive value (81%) were obtained. CONCLUSION: The data suggest that an ARR >or= 69 strongly indicates PA in Japanese patients with hypertension being treated with antihypertensive agents.

Associations of hypertension and its complications with variations in the xanthine dehydrogenase gene.

Hyperuricemia and oxidative stress participate in the pathophysiology of hypertension and its complications. Xanthine dehydrogenase (XDH) produces urate and, in its oxidase isoform, reactive oxygen species. Here we have studied whether or not the genetic variations in XDH could be implicated in hypertension and its complications. By sequencing the promoter region and all exons of XDH in 48 subjects, we identified three missense mutations (G172R, A932T, N1109T) in a heterozygous state in addition to 34 variations, including 15 common single nucleotide polymorphisms (SNPs). The three missense mutations and eight common SNPs (11488C>G, 37387A>G, 44408A>G, 46774G>A, 47686C>T, 49245A>T, 66292C>G, and 69901A>C) were genotyped in 953 hypertensive Japanese subjects and in 1,818 subjects from a general Japanese population. Four hypertensive patients with rare missense mutations (G172R or N1109T) in homozygous form had severe hypertension. Multivariate logistic regression analysis showed a significant association of three SNPs with hypertension in men: 47686C>T (exon 22, odds ratio [OR]: 1.52, p = 0.047) and 69901A>C (intron 31, OR: 3.14, p = 0.039) in the recessive model, and 67873A>C (N1109T) (exon 31, OR: 1.84, p = 0.018) in the dominant model. After full adjustment for all confounding factors, only one polymorphism (69901A>C) was found to be associated with carotid atherosclerosis in the dominant model (p = 0.028). Multiple logistic regression analysis showed that one SNP (66292C>G) was significantly associated with chronic kidney disease (CKD: estimated creatinine clearance < 60 ml/min) in the recessive model (p = 0.0006). Our results suggest that genetic variations in XDH contribute partly to hypertension and its complications, including atherosclerosis and CKD.

Decreased coronary flow reserve in haemodialysis patients.

BACKGROUND: Coronary flow reserve (CFR) reflects the functional capacity of microcirculation to adapt to blood demand during increased cardiac work. METHODS: Forty-one patients who had already undergone coronary angiography were studied. They consisted of 21 haemodialysis patients with no significant left anterior descending coronary artery (LAD) stenosis and 20 non-renal failure patients without LAD stenosis. We performed transthoracic Doppler recording of diastolic coronary flow velocity in the LAD at baseline and after maximal vasodilatation by adenosine triphosphate (ATP) infusion. CFR was defined as the ratio of hyperaemic to basal averaged peak flow velocity. RESULTS: Although the peak coronary velocities during hyperaemia were similar between the two groups, CFR was smaller in haemodialysis (HD) patients than in control subjects (1.96 +/- 04 versus 2.3 +/- 0.5, P = 0.001) due to the higher baseline peak coronary velocities in the former. CONCLUSIONS: The elevated baseline peak coronary velocity may be caused by cardiac hypertrophy and anaemia in HD patients.

Brain natriuretic peptide in hemodialysis patients: predictive value for hemodynamic change during hemodialysis and cardiac function.

BACKGROUND: Though brain natriuretic peptide (BNP) is widely used as a clinical marker of cardiac function, there is considerable confusion in the interpretation of its value in hemodialysis (HD) patients whose BNPs are often elevated without cardiac diseases. The aim of the present study is to examine the predictive value of BNP for blood pressure (BP) fall during HD and cardiac function. METHODS: Subjects consisted of 205 (160 males, 45 females; age 66.5 +/- 10.5 years) consecutive uremic patients requiring maintenance HD who were admitted to our hospital during 2001-2004. One hundred and eleven cases had a history of ischemic heart disease. We measured BNP in all cases and collected clinical data including age, sex, duration of HD, blood examination and echocardiography. RESULTS: BNP of all 205 cases ranged from 6 to 16,097 pg/ml (median 831). During HD, the average BP change was -24.5 +/- 20.5 mm Hg, and 111 cases showed a systolic BP reduction >20 mm Hg. BNP did not predict the degree of BP fall. After adjusting confounding factors, the presence of ischemic heart disease, ultrafiltration rate, systolic BP before HD and serum sodium concentration showed a significant correlation with BP change (t = -2.84, -2.76, -4.68 and 2.90; p = 0.005, <0.01, <0.0001 and <0.005, respectively). In relation to echocardiographic indices, BNP >785 pg/ml could predict left ventricular dysfunction (fractional shortening of the left ventricle <30%, sensitivity 73%, specificity 65%). CONCLUSION: The level of BNP could not predict BP fall during HD. However, BNP is a good indicator of cardiac function even in uremic patients.

Relationship between insulin resistance and the renin-angiotensin system: analysis for patients with essential and renovascular hypertension.

Insulin resistance is frequently observed in patients with essential hypertension (EHT), and the renin-angiotensin system (RAS) has been demonstrated to modulate the status of insulin resistance. The aims of present study are to investigate the relationship between systemic RAS and insulin resistance in 82 patients with EHT and compare the impact of RAS to insulin resistance with 10 renovascular hypertension (RVHT) patients who have a highly activated systemic RAS. From patients who were admitted to our hospital, patients with overt diabetes and hypertensives who had secondary HT except RVHT or chronic renal failure were excluded. Plasma renin activity (PRA) was used as an indicator of systemic RAS activity. HOMA-R as an index of insulin resistance and sum of immunoreactive insulin (IRI) during glucose tolerance test (sigmaIRI) and IRI at 120 minutes (IRI120) were used as indices of hyperinsulinemia. In the EHT patients, circulating PRA showed an independent relationship with IRI120 and sigmaIRI after adjusting confounding factors (IRI120: t = 2.70, p = 0.01, sigmaIRI: t = 3.05, p < 0.001). Excluding patients who were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blocker (ARBs), the relationship remained in univariate linear regression; after adjustment for confounding factors, PRA showed a tendency to be correlated with sigmaIRI. However, there was no significant relationship between PRA and indices of insulin resistance and hyperinsulinemia in patients with RVHT. In conclusion, the systemic RAS may modulate insulin sensitivity in EHT patients.

Midregional proadrenomedullin reflects cardiac dysfunction in haemodialysis patients with cardiovascular disease.

BACKGROUND: Although adrenomedullin is an indicator of cardiac dysfunction in haemodialysis patients, the clinical significance of midregional proadrenomedullin has not been elucidated. Objectives. We evaluated whether midregional proadrenomedullin reflects cardiac dysfunction, systemic inflammation or blood volume in haemodialysis patients. METHODS: Plasma midregional proadrenomedullin, C-reactive protein and delta body weight (indicating excessive blood volume), and two-dimensional as well as Doppler echocardiographic variables were measured just before haemodialysis in 70 patients with cardiovascular disease. RESULTS: The median value of midregional proadrenomedullin was 1.93 nmol/l before haemodialysis, and these levels were significantly reduced following haemodialysis. Log [midregional proadrenomedullin] was positively correlated with left ventricular end-systolic volume index, diameter of inferior vena cava, C-reactive protein and delta body weight (r = 0.328, r = 0.421, r = 0.356, r = 0.364), and negatively with blood pressure, deceleration time of an early diastolic filling wave, pulmonary venous flow velocity ratio and left ventricular ejection fraction (r = -0.330, r = -0.324, r = -0.479, r = -0.373). Multivariate regression analysis revealed that pulmonary venous flow velocity ratio, diameter of inferior vena cava and C-reactive protein were independently related factors for midregional proadrenomedullin concentration. CONCLUSION: Plasma midregional proadrenomedullin levels increase in association with cardiac dysfunction, systemic inflammatory status and systemic blood volume in haemodialysis patients with concomitant cardiovascular disease.

Effect of early nephrology referral on the initiation of hemodialysis and survival in patients with chronic kidney disease and cardiovascular diseases.

BACKGROUND: The timing of referral to nephrologists is highly variable in patients with chronic kidney disease (CKD). The impact of early referral on the timing of hemodialysis (HD) and mortality in the patients with CKD and cardiovascular diseases (CVD) was evaluated in this present study. METHODS AND RESULTS: A total of 366 patients with CKD and CVD began HD at the National Cardiovascular Center between 1983 and 2003, and survival was followed until 2005. The times between the first evaluation by a nephrologist and the date of the first HD were categorized as late (LR <6 months) or early (ER > or =6 months) referral. Patients were classified into the ER (n=194) and LR (n=172) groups. Clinical data and renal function were not different. In the LR group, the renal function declined more rapidly and the duration between the first visit to the hospital and the first HD was shorter than the ER group. The survival rate after the initiation of HD was better in the ER group. Age, pre end-stage renal disease therapy and cardiac function had a significant impact on survival. CONCLUSIONS: Early nephrology referral is important and necessary for for patients with CKD and CVD in terms of a better renal prognosis and survival.

Reverse white-coat effect as an independent risk for microalbuminuria in treated hypertensive patients.

BACKGROUND: The influence of the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' on hypertensive target organ damage has not been fully elucidated. The present study assessed the hypothesis that this phenomenon may specifically associate with microalbuminuria, a marker of early renal damage, in treated hypertension. METHODS: A total of 267 treated essential hypertensive patients (133 men and 134 women; mean age, 66 years) without renal insufficiency or macroalbuminuria were enrolled in this study. Patients were classified into three groups by the difference between office and day-time ambulatory systolic blood pressure (BP) levels; i.e. subjects with white-coat effect (W group: office--day-time systolic BP > or =20 mmHg, n = 48), with reverse white-coat effect (R group: office - day-time systolic BP < - 10 mmHg, n = 43) and without white-coat or reverse white-coat effect (N group: -10 mmHg < or = office--day-time systolic BP <20 mmHg, n = 176). The urinary albumin (U-Alb) level was measured as the albumin to creatinine excretion ratio in the urine. Microalbuminuria was defined as U-Alb of > or =30 and <300 mg/g Cr. RESULTS: R group had a well-controlled office BP (130/77 mmHg), but their day-time BP (148/87 mmHg) was elevated compared with the other two groups. The levels of U-Alb excretion in N group, W group and R group were 12.3 (8.4, 25.6), 16.0 (10.5, 31.7) and 24.3 (10.2, 79.7) mg/g Cr [median (interquartile range)], respectively. Both U-Alb level and prevalence of microalbuminuria were significantly greater in R group than in N group. Multivariate analyses revealed that the presence of reverse white-coat effect, but not white-coat effect, was a significant predictor for microalbuminuria, independent of various clinical variables including ambulatory BP levels (odds ratio 2.63 vs N group, P = 0.02). CONCLUSION: These findings suggest that the presence of reverse white-coat effect may be an independent risk for early renal damage in treated hypertensive patients.

Masked hypertension and target organ damage in treated hypertensive patients.

BACKGROUND: Recent studies have shown that an elevated ambulatory or home blood pressure (BP) in the absence of office BP-a phenomenon called masked hypertension-is associated with poor cardiovascular prognosis. However, it remains to be elucidated how masked hypertension modifies target organ damage in treated hypertensive patients. METHODS: A total of 332 outpatients with chronically treated essential hypertension were enrolled in the present study. Patients were classified into four groups according to office (<140/90 or >or=140/90 mm Hg) and daytime ambulatory (<135/85 or >or=135/85 mm Hg) BP levels; ie, controlled hypertension (low office and ambulatory BP), white-coat hypertension (high office but low ambulatory BP), masked hypertension (low office but high ambulatory BP), and sustained hypertension (high office and ambulatory BP). Left ventricular mass index, carotid maximal intima-media thickness, and urinary albumin levels were determined in all subjects. RESULTS: Of the patients, 51 (15%), 65 (20%), 74 (22%), and 142 (43%) were identified as having controlled hypertension, white-coat hypertension, masked hypertension, and sustained hypertension, respectively. Left ventricular mass index, maximal intima-media thickness, and urinary albumin level in masked hypertension were significantly higher than in controlled hypertension and white-coat hypertension, and were similar to those in sustained hypertension. Multivariate regression analyses revealed that the presence of masked hypertension was one of the independent determinants of left ventricular hypertrophy, carotid atherosclerosis, and albuminuria. CONCLUSIONS: Our findings indicate that masked hypertension is associated with advanced target organ damage in treated hypertensive patients, comparable to that in cases of sustained hypertension.

Renal function in patients with abdominal aortic aneurysm. Comparison with hypertensive patients.

AIMS: Renal dysfunction occurs occasionally after the repair of abdominal aortic aneurysm (AAA), and preoperative renal function is considered as one of the potential causes. The present study was designed to evaluate and compare renal function and risk factors of AAA patients with those of hypertensive patients. METHODS: We prospectively examined 95 patients with AAA and 72 patients with essential hypertension (HT) without other cardiovascular diseases (CVD). Renal function, urinary albumin excretion (UAE) and renal scintigraphy were compared. Kidney size was calculated using ultrasonography. RESULTS: Serum creatinine and creatinine clearance in AAA patients was worse than in HT patients. Smoking status was more apparent in AAA patients. Renal artery stenosis occurred in 8 patients with AAA. Renal scintigraphy showed normal function in 19%, hypofunction in 69% and severe dysfunction in 12% of the AAA patients, and normal function in 42% and hypofunction in 58% of the HT patients (p < 0.0001). Multivariate linear regression analysis showed that renal function was related to age, UAE, CVD, smoking status and kidney size for all patients, UAE, CVD, smoking status and kidney size for AAA patients, and age and kidney size for HT patients. CONCLUSION: Renal function of AAA patients was worse than HT patients without other CVD. The risk factors for renal dysfunction were different between AAA and HT patients. These preoperative conditions may relate to the postoperative renal dysfunction seen in AAA patients.

Positive correlations between cerebral choline and renal dysfunction in chronic renal failure.

INTRODUCTION: Cerebral metabolism in chronic renal failure (CRF) patients has not been fully evaluated. This study examined cerebral metabolites in CRF, using proton magnetic resonance spectroscopy (MRS). METHODS: Subjects comprised 19 CRF patients and 21 healthy volunteers. Spectra were acquired from voxels of interest positioned in the parietal gray and white matter, and concentrations of the following cerebral metabolites were measured: N-acetyl group (NA), creatine + phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol and glutamate + glutamine. Among the 19 CRF patients, 9 who were started on hemodialysis (HD) underwent careful follow-up. Proton MRS was performed before and about 2 weeks after starting HD. In six patients in whom follow-up was possible, a third MRS was performed after about 18 months. RESULTS: The NA/Cr ratio was not significantly changed in CRF. However, elevations in the Cho/Cr ratio were found in both gray and white matter compared with controls. To the best of our knowledge, this is the first report of positive correlations between the Cho/Cr ratio in both regions and serum osmotic pressure. Compared with baseline data, no significant changes in cerebral metabolite ratios were found about 2 weeks after starting HD. About 18 months after starting HD, however, the elevated Cho/Cr ratio was significantly reduced in the gray matter and tended to be reduced in the white matter. CONCLUSIONS: Cho appear to play an important role in the regulation of cerebral metabolism to compensate for alterations in serum osmotic pressure in CRF, and HD may correct this abnormal cerebral metabolism.

Relationship between renal artery stenosis and intrarenal damage in autopsy subjects with stroke.

BACKGROUND: In patients with cardiovascular disease (CVD), renal dysfunction is a risk factor for the prognosis, but substantial evidence is still lacking about the relationship between clinical characteristics and renal histology. The aim of our study was to evaluate the relationship between the extent of renal parenchymal damage, renal artery stenosis (RAS) and clinical characteristics in autopsy subjects with stroke. METHODS: During the 17-year period 1980-1997, 2167 subjects were autopsied at the National Cardiovascular Center. We studied retrospectively all the autopsy cases aged 40 years and older who had a history of stroke. Thus, 346 subjects remained and they were classified into two groups. Thirty-six subjects had RAS (group A). Three hundred and ten subjects had no RAS, and we randomly chose 102 subjects among them (group B). We evaluated renal parenchymal damage using a semi-quantitative chronic damage score. RESULTS: The average overall chronic damage score was significantly higher in the stenosed kidneys of group A than in the non-stenosed kidneys of group B (9.0+/-2.6 vs 7.0+/-2.7). The contralateral kidneys of group A had a tendency to have milder renal damage than stenosed kidneys. Furthermore, the total score was higher in the subjects with hypertension, diabetes mellitus, proteinuria, renal insufficiency and CVD than in the subjects without such complications. The total score had a significant association with RAS, proteinuria, renal insufficiency, CVD and weight of the kidney. CONCLUSIONS: In autopsy subjects with stroke, we demonstrated that co-existing renal parenchymal damage was more severe in the subjects with RAS, hypertension, diabetes mellitus, proteinuria and renal insufficiency than those without such complications. The presence of RAS, impaired renal function and proteinuria was closely correlated with the severity of renal parenchymal damage.

Primary aldosteronism combined with preclinical Cushing's syndrome in an elderly patient.

Pre-clinical Cushing's syndrome (pre-CS) is sometimes seen with adrenal cortical tumors. An 80-year-old woman had severe hypertension and hypokalemia, the typical clinical features of primary aldosteronism, but detailed hormonal examinations revealed the accompanying pre-CS. After adrenalectomy by laparoscopy, her blood pressure was remarkably reduced and the hypokalemia also recovered. The tumor consisted of mostly light clear cells and scattered dark compact cells resembling islands. Abundant expression of cytochrome P450 aldosterone synthase in the clear cells and cytochrome P450 11beta-hydroxylase in the dark cells was detected by immunohistochemical studies, which confirmed that clear cells can produce aldosterone and compact cells can produce cortisol.