慢性肾功能不全病人红细胞内游离原卟啉测定

目的：了解肾性贫血病人骨髓细胞内可染铁明显增加的原因。方法：采用免疫荧光分光光度法测定４０ 例慢性肾功能不全病人红细胞内游离原卟啉（ＦＥＰ）,并以３１ 例正常人作为对照。结果：显示慢性肾功能不全组ＦＥＰ／Ｈｂ 及ＦＥＰ／ＲＢＣ水平（２．８５±１．２９ μｇ／Ｈｂ．ｇ;８２．４５±３４．６５ μｇ／ＲＢＣ．ｄｌ）,显著高于正常对照组（１．７６±０．７１ μｇ／Ｈｂ．ｇ;５１．１６±２０．２５ μｇ／ＲＢＣ．ｄｌ）Ｐ＜ ０．００１。而全血ＦＥＰ值两组之间差异无显著性（慢性肾功能不全组：２１．０４±１０．８０ μｇ／ｄｌ全血;正常组：２４．７８±９．８３ μｇ／ｄｌ全血, Ｐ＞ ０．０５）。同时,慢性肾功能不全组血清铁蛋白水平（２３８．５６±１６９．５９ μｇ／Ｌ）显著高于正常对照组（１１２．５１±７１．５４μｇ／Ｌ,Ｐ＝ ０．０００２）。而且反复接受输血组与未曾输血组之间差异无显著性。结论：肾性贫血具有ＦＥＰ增高及铁负荷增加等特点。     

Potential for use of pulse wave analysis in determining the interaction between sildenafil and glyceryl trinitrate

BACKGROUND: The early part of the central aortic pressure pulse, with amplitude (PI - Pd), is generated by left ventricular ejection, while the latter part (or augmented pressure), with amplitude (Ps - Pi), is generated by the reflected wave arriving during systole. The effects of arterial vasodilator agents, especially nitrates, on central aortic systolic blood pressure are grossly underestimated by sphygmomanometric measurements of brachial artery pressure. HYPOTHESIS: The objective of this study was to investigate the potential for use of central arterial pulse wave analysis, obtained noninvasively from the radial pulse, in determining the interaction between sildenafil and the nitric oxide donor drug glyceryl trinitrate (GTN). METHODS: Central aortic pressure waveforms were generated from noninvasively measured radial artery pressure wave-forms and subjected to pulse wave analysis to determine the interaction between sildenafil and transdermally applied GTN. RESULTS: Transdermal GTN (2.5, 5.0, and 15 mg per 24-h patches) alone caused no consistent change in sphygmomanometer-determined systolic or diastolic pressures, but there was a consistent, dose-related fall in amplitude of the augmented systolic pressure, (Ps - Pi), of 4.0, 7.0, and 11 mmHg, respectively, with little change in diastolic pressure. The 2.5 mg patch caused a fall of 4.0 mmHg in aortic systolic pressure, while augmentation index (AIx) fell from 20 to 11% and pulse pressure fell 18%. When oral sildenafil (50 mg) was administered after GTN (2.5 mg), aortic systolic pressure fell another 4.0 mmHg. This decrease in systolic pressure caused a fall in AIx to almost 0.0%; pulse pressure fell another 9.0%. CONCLUSION: These modifications in aortic systolic and pulse pressure are due primarily to reduction in wave-reflection amplitude and are not detected by sphygmomanometer-measured brachial artery pressure.     

Arterial stiffness is associated with increase in blood pressure over time in treated hypertensives

Arterial stiffness is associated with incident hypertension. We hypothesized that measures of arterial stiffness would predict increases in systolic (SBP), mean (MAP), and pulse pressure (PP) over time in treated hypertensives. Blood pressure (BP) was measured a mean of 8.5 ± 0.9 years apart in 414 non-Hispanic white hypertensives (mean age, 60 ± 8 years; 55% women). The average of three supine right brachial BPs was recorded. Measures of arterial stiffness, including carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), and central pulse pressure (CPP), were obtained at baseline by applanation tonometry. We performed stepwise multivariable linear regression analyses adjusting for potential confounders to assess the associations of arterial stiffness parameters with BP changes over time. SBP, MAP, and PP increased in 80% of participants. After adjustment for covariates listed, cfPWV (m/s) was associated with increases in SBP (β ± standard error [SE], 0.71 ± 0.31) and PP (β ± SE, 1.09 ± 0.27); AIx (%) was associated with increases in SBP (β ± SE, 0.23 ± 0.10) and MAP (β ± SE, 0.27 ± 0.07); and CPP (mmHg) was associated with increases in SBP (β ± SE, 0.44 ± 0.07), MAP (β ± SE, 0.24 ± 0.05), and PP (β ± SE, 0.42 ± 0.06) over time (P ≤ .02 for each). In conclusion, arterial stiffness measures were associated with longitudinal increases in SBP, MAP, and PP in treated hypertensives.     

Increased Arterial Augmentation and Augmentation Index as Surrogate Parameters for Arteriosclerosis in Subjects with Diabetes Mellitus and Nondiabetic Subjects with Cardiovascular Disease

Background

Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to compare these parameters in diabetic subjects and nondiabetic cardiovascular risk subjects with healthy control subjects.

Methods

One hundred sixty-six nonsmoking subjects aged between 35 and 70 years were included in the study, which included 100 subjects with cardiovascular disease but not diabetes (mean age 62.73±8.75 years), 33 subjects with type 2 diabetes (66.58±2.69 years), and 33 healthy controls (51.89±8.91 years). In these subjects, arterial stiffness was measured by the difference between the second and the first systolic peak of the central pressure waveform, and the Aix was calculated as the percentage of Aix from pulse pressure.

Results

Arterial augmentation was increased in subjects with diabetes (DM) with 10.21±6.97 mm Hg and in subjects with cardiovascular disease but not diabetes (CV) with 10.74±5.29 mm Hg in comparison to healthy controls (C) with 6.59±3.97 mm Hg (p < 0.0005 DM vs C; p < 0.00005 CV vs C). Moreover, Aix was increased with 26.00±9.91% in CV subjects compared to healthy controls with 19.84±9.37% (p < 0.02 CV vs C). The augmentation index was increased with 21.12±11.21% in subjects with type 2 diabetes mellitus compared to controls, but failed to be statistically significant. There was no statistical significance in arterial augmentation or the augmentation index between CV and diabetic subjects.

Conclusion

The results of our study revealed a comparable increased augmentation index as a surrogate measure of arterial stiffness and arteriosclerosis in subjects with diabetes mellitus and in nondiabetic subjects with cardiovascular disease.     

Baseline Urinary Angiotensinogen Excretion Predicts Deterioration of the Kidney Function in Patients with Chronic Kidney Disease

Objective The intrarenal renin-angiotensin system (RAS) is activated in patients with chronic kidney disease (CKD), and urinary angiotensinogen (AGT) levels, a surrogate marker of the intrarenal RAS activation, are associated with blood pressure (BP) and urinary albumin excretion. In addition, it has been shown that changes in urinary AGT levels correlate with annual changes in the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes and that elevated levels of urinary AGT in type 2 diabetic patients with albuminuria are a high-risk factor for worsening renal and cardiovascular complications. However, whether or not baseline urinary AGT levels predict deterioration of the kidney function in all patients with CKD is unclear. Methods We recruited 62 patients with CKD whose eGFR was ＞15 mL/min/1.73 m². We performed 24-hour ambulatory BP monitoring at 30-min intervals and daily urinary collection to examine the urinary AGT levels and albumin excretion and measured the levels of plasma angiotensin II (Ang II), a surrogate marker of circulating RAS. In addition, annual changes in the eGFR were followed up for 3.4±1.5 years. Results Annual changes in the eGFR were significantly and negatively associated with urinary AGT levels (r=-0.31, p=0.015) as well as the age, systolic BP, and urinary albumin levels. In contrast, annual changes in the eGFR were not correlated with plasma Ang II levels. Furthermore, when dividing patients into quartiles according to urinary AGT levels, patients with the highest urinary AGT levels showed a progressive decline in the eGFR. Conclusion These results suggest that elevated baseline urinary AGT levels can predict renal dysfunction in patients with CKD.     

中心动脉压及其相关指标的临床意义

中心动脉压不同于肱动脉血压,其与一些相关指标是心血管疾病及事件的真正关联因素。在许多生理及病理状态下中心动脉压及其相关指标会发生变化,检测中心动脉压及其相关指标具有重要的临床意义。     

Progression of Renal Dysfunction in Patients with Cardiovascular Disease

It has been established that patients with chronic kidney disease (CKD) suffer from frequent cardiovascular events. On the other hand, recent studies suggest that renal damage tends to worsen in patients with cardiovascular diseases (CVD). Although the mechanisms for the cardiorenal association are unclear, the presence of arteriosclerotic risk factors common to both CVD and CKD is important. In arteriosclerosis, vascular derangement progresses not only in the heart but also in the kidney. In addition, heart failure, cardiac catheterization and hesitation of medical treatments due to renal dysfunction may explain the progression of renal damage. Therefore, the goal of treatments is a total control of arteriosclerotic risk factors. Medication should be selected among agents with protective effects on both heart and kidney. It is important to always consider the presence of CKD for the treatment of the cardiovascular disease and strictly control the risk factors.Key Words: CKD, angiotensin II, aldosterone, ARB, hypertension.     

Hypertension Management in Patients with Chronic Kidney Disease

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.     

Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness

Antihypertensive agents may, even within the same class, exert variable effects on arterial stiffness variables. Nebivolol could have a better impact than atenolol on arterial stiffness, by increasing the bioavailability of endothelium-derived nitric oxide. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) increase plasma renin activity (enhancing the production of angiotensin II via non-ACE-related pathways) whereas aliskiren does not, potentially affecting central hemodynamics differently. We compared the effects of two renin-angiotensin-aldosterone system (RAAS) inhibitors (quinapril and aliskiren) and 2 beta-blockers (atenolol and nebivolol) on arterial stiffness variables. Treatment-naïve patients (n = 72; 68.1% males; age, 47.6 ± 10.6 years) with uncomplicated stage I-II essential hypertension were randomly assigned to quinapril, aliskiren, atenolol, or nebivolol for 10 weeks. Central systolic and diastolic blood pressure (BP), central pulse pressure (PP), augmentation index (AIx), and pulse wave velocity (PWV) were measured at baseline, 2, and 10 weeks. The same measurements were performed in 20 normotensive subjects (65.0% males; age, 40.0 ± 8.9 years). Peripheral and central systolic and diastolic BP, peripheral PP, and PWV were significantly and similarly reduced by all agents. However, PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol. Central PP and AIx decreased in patients on quinapril, aliskiren, and nebivolol but did not change in those taking atenolol. The decrease in central PP and AIx did not differ between patients on quinapril, aliskiren, and nebivolol. Despite similar reductions in peripheral BP, atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics. Aliskiren exerts similar effects on markers of arterial stiffness as quinapril. The clinical relevance of these differences remains to be established.     

Association of BP with Death,Cardiovascular Events,and Progression to Chronic Dialysis in Patients with Advanced Kidney Disease

Background and objective

The optimal BP target to reduce adverse clinical outcomes in patients with CKD is unclear. This study examined the relationship between BP and death, cardiovascular events (CVEs), and kidney disease progression in patients with advanced kidney disease.

Design, setting, participants, & measurements

The relationship of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) with death, CVE, and progression to long-term dialysis was examined in 1099 patients with advanced CKD (eGFR≤30 ml/min per 1.7 3m²; not receiving dialysis) who participated in the Homocysteine in Kidney and ESRD study. That study enrolled participants from 2001 to 2003. Cox proportional hazard models were used to examine the association between BP and adverse outcomes.

Results

The mean±SD baseline eGFR was 18±7 ml/min per 1.73 m². During a median follow-up of 2.9 years, 453 patients died, 215 had a CVE, and 615 initiated long-term dialysis. After adjustment for demographic characteristics and confounders, SBP, DBP, and PP were not associated with a higher risk of death. SBP and DBP were also not associated with CVE. The highest quartile of PP was associated with a substantial higher risk of CVE compared with the lowest quartile (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.10 to 2.52). The highest quartiles of SBP (HR, 1.28; 95% CI, 1.01 to 1.61) and DBP (HR, 1.36; 95% CI, 1.07 to 1.73), but not PP, were associated with a higher risk of progression to long-term dialysis compared with the lowest quartile.

Conclusions

In patients with advanced kidney disease not undergoing dialysis, higher PP was strongly associated with CVE whereas higher SBP and DBP were associated with progression to long-term dialysis. These results suggest that SBP and DBP should not be the only factors considered in determining antihypertensive therapy; elevated PP should also be considered.     

The Relationship Between Some of the Cardiovascular Risk Factors and Arterial Stiffness Parameters in Essentially Hypertensive Patients

Hypertensive patients have strong evidence of endothelial dysfunction. We aimed to explore the relationships between cardiovascular risk factors and arterial stiffness parameters in hypertensive patients. The study population included 109 hypertensive patients (63 females, 46 males). Arterial stiffness measures including pulse wave velocity, augmentation index, and central aortic pressure were applied. Augmentation index and central aortic pressure were found to be significantly higher (P < .001 and P = .03, respectively) in women. The higher augmentation index and central aortic pressure values were observed in women than in men. These data offer new evidences for the role of sex hormones in the pathogenesis of atherosclerosis in women.     

Renal Dysfunction in Patients with Left Ventricular Assist Device

Late-stage heart failure and renal dysfunction are often seen in conjunction. Cardiorenal syndrome (CRS) describes the complex interaction between the two disease states. Early literature described the pathophysiology of CRS as related only to reduced cardiac output and decreased renal perfusion. Recent literature suggests a more multifaceted mechanism. Left ventricular assist devices (LVAD), used as bridge-to-transplant and destination therapy in patients with heart failure, impact not only cardiac function but also renal function, especially in those patients with preoperative renal dysfunction. The mechanism by which LVAD implantation affects renal function is complex and understated in early literature. In this review, we discuss the pathogenesis of CRS, the impact of preoperative renal dysfunction in patients undergoing LVAD implantation, and the effect of LVAD implantation on postoperative renal function.     

Nonprogressive Kidney Dysfunction and Outcomes in Older Adults with Chronic Kidney Disease

OBJECTIVES: To determine whether a subgroup of patients with severe but nonprogressive renal dysfunction exist and to characterize this subgroup. DESIGN: Retrospective longitudinal monocentric cohort study. SETTING: Nephrology clinic for chronic kidney disease (CKD). PARTICIPANTS: Between January 1998 and December 2004, 177 consecutive patients aged 80 and older were referred for the first time to nephrology for CKD. MEASUREMENTS: The characteristics of patients with nonprogressive or progressive CKD (estimated glomerular filtration rate (eGFR) decline of < and ≥1 mL/min per 1.73 m² per year, respectively) were observed and analyzed, and their risk of dying or requiring dialysis was determined. After exclusion of subjects requiring immediate dialysis or followed up for less than 6 months, 138 patients remained eligible for analysis. RESULTS: In the study cohort (initial mean eGFR 31.8 mL/min per 1.73 m², median follow‐up 47 months), patients were more likely to require dialysis than to die; 36% of patients had nonprogressive CKD. This characteristic, predicted by low proteinuria, lack of hypertension, and low cardiovascular comorbidity, was the strongest predictor of global survival. In progressors, two independent covariates (eGFR <30 mL/min per 1.73 m² and hemoglobin ≤11 g/dL at inclusion) predicted the risk of requiring dialysis. CONCLUSION: More than one‐third of subjects aged 80 and older referred to a nephrology center had severe but nonprogressive kidney dysfunction. This subgroup had a lower mortality rate than those with progressive kidney dysfunction. Simple covariates (low proteinuria, lack of hypertension, low cardiovascular comorbidity) predicted nonprogression of CKD. Distant nephrology follow‐up of such patients may be sufficient.     

慢性肾功能不全与心血管疾病的关系

心血管疾病是造成终末期肾脏病患者死亡的主要原因,除了一般人群常见的心血管疾病危险因素(如高血压、糖尿病、高脂血症、吸烟、家族史、年龄、性别)外,目前认为慢性肾脏疾病相关危险因素如贫血、高同型半胱氨酸血症、高磷血症、低蛋白血症、微炎症状态、氧化应激等与终末期肾脏疾病患者心血管疾病的发生有关。     

Association Between Nondipper Behavior and Serum Calcium in Hypertensive Patients with Mild-to-Moderate Chronic Renal Dysfunction

A nondipping BP pattern has been shown to be predictive of end-organ damage, cardiovascular events, and mortality. The mechanisms of blunted nocturnal BP fall are multifactorial. We assessed whether total corrected serum calcium and ionic calcium (iCa) are associated with a blunted nocturnal BP fall in both treated and untreated hypertensive patients with stages 1–3 of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI). Clinical data and 24-hour ambulatory blood pressure monitoring were obtained in a cohort of 231 essential hypertensive patients. Among the entire cohort, 107 were nondippers and 124 were dippers. Only in nondippers, we found significant correlations between iCa and 24-hour systolic blood pressure (SBP; r = 0.21, P < .03), diurnal SBP (r = 0.21, P < .03), and 24-hour pulse pressure (PP; r = 0.23, P < .02). The ambulatory arterial stiffness index (AASI) was significantly related with 24-hour PP in both dippers and nondippers after adjusting for age. Both AASI and 24-hour PP were higher in nondippers than in dippers. In addition, in nondippers, the prevalence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m² was higher than in dippers (50% vs. 33.7%, P < .02). Logistic regression showed that patients with eGFR ≥60 mL/minute/1.73 m² had lower risk of nondipper status than patients with eGFR <60 mL/minute/1.73 m² (odds ratio = 2.445; 95% confidence interval = 1.398–4.277, P < .002). In conclusion, serum iCa could participate in the pathogenesis of nondipping pattern. Increased large artery stiffness may be a mechanism of the deleterious influence of nondipping on cardiovascular outcome. Hypertensive subjects with stage 3 of NKF KDOQI had a greater loss of circadian BP rhythm than those in stages 1 and 2.     

Analysis of Factors that Affect Short-Term Blood Pressure Variability in Patients with Chronic Renal Failure

Recent reports suggest the relationship of short-term blood pressure (BP) variability to cardiovascular target organ damage. In this study, short-term BP variability was assessed as the standard deviation of daytime and nighttime BP in 36 hospitalized patients with chronic renal failure (CRF) who underwent ambulatory BP monitoring. Positive correlations were observed between body mass index (BMI) and daytime systolic and diastolic BP variability, BMI and nighttime diastolic BP variability, cholesterol and daytime systolic BP variability, cholesterol and nighttime systolic and diastolic BP variability, nocturnal decline in BP and nighttime diastolic BP variability, and plasma concentration of norepinephrine (p-NE) and nighttime systolic BP variability. In multivariate linear regression analyses, BMI showed the strongest association with daytime and nighttime diastolic BP variability (p < .005 and p < .05). On the other hand, cholesterol and p-NE were the primary determinants of daytime and nighttime systolic BP variability, respectively (p < .01 and p < .0005). Interestingly, CRF patients with ischemic heart disease (IHD) had significantly increased daytime systolic and diastolic BP variability and nighttime systolic BP variability (p < .05 or less). Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor of IHD in patients with CRF (odds ratio 1.50 [95% confidence interval 1.01 to 2.25]; p < .05). Taken together, short-term BP variability is suggested to be affected by BMI, cholesterol, and p-NE in CRF patients. Furthermore, sympathetic nerve overactivitymay be involved in cardiovascular complications in CRF patients through the increase in nighttime systolic BP variability.