Chronic kidney disease,mortality, and treatment strategies among patients with clinically significant coronary artery disease

Cardiovascular disease is an important cause of mortality among patients with chronic kidney disease (CKD). This study describes associations between CKD, cardiac revascularization strategies, and mortality among patients with CKD and cardiovascular disease. All patients undergoing cardiac catheterization at Duke University Medical Center (1995 to 2000) with documented stenosis > or =75% of at least one coronary artery and available creatinine data were included. CKD was staged using creatinine clearance (CrCl) derived from the Cockcroft-Gault formula (normal, > or = 90 ml/min; mild, 60 to 89 ml/min; moderate, 30 to 59 ml/min; severe, 15 to 29 ml/min). Cox proportional-hazard regression estimated the relationship between clinical variables, including CrCl and percutaneous coronary artery intervention (PCI), coronary artery bypass grafting (CABG), medical management, and patient survival. There were 4584 patients included, and 24% had CrCl <60 ml/min. Each 10-ml/min decrement in CrCl was associated with an increase in mortality (hazard ratio, 1.14; P < 0.0001). CABG was associated with a survival benefit among patients with both normal renal function and patients with CKD compared with medical management. In patients with normal renal function, CABG was not associated with survival benefit over PCI. However, in patients with CKD, CABG was associated with improved survival. PCI was associated with a survival benefit compared with medical management among patients with normal, mildly, and moderately impaired renal function. Among patients with severe CKD, PCI was not associated with improved survival. CABG is associated with greater mortality reduction than PCI in severe CKD.     

Serum uric acid levels show a 'J-shaped' association with all-cause mortality in haemodialysis patients.

BACKGROUND: Although elevated serum levels of uric acid are common in patients with kidney disease or in those receiving maintenance dialysis therapy, the clinical impact of uric acid on mortality in haemodialysis (HD) patients remains unclear. This work was designed to explore the predictive value of serum uric acid levels on all-cause mortality of HD patients. METHODS: We retrospectively analysed mortality rates in 146 chronic HD patients that were treated with HD three times per week at our HD unit for a period of one full year. The analysed parameters included demographic characteristics, aetiology of end-stage renal disease, co-morbid conditions, duration (at least 1 year) and delivered dose of HD, normalized protein catabolic rate, serum albumin concentration, haematocrit, serum uric acid (UA) levels and other laboratory parameters. A multivariate Cox proportional hazards model, which included adjustment for the above factors, was applied to identify the predictive value of UA levels on patient mortality. RESULTS: A Cox proportional hazards model revealed that decreased serum albumin, underlying diabetic nephropathy (DMN) and UA groups (< or =20th, 20-80th and > or =80th percentiles; P = 0.016) were all significant, independent predictors of all-cause mortality in HD patients. The hazard ratios of death were: serum albumin (per 0.5 g/dl decrease), 3.10 [95% confidence interval (95% CI), 1.80-5.34, P < 0.001]; DMN (vs non-DMN), 3.47 (95% CI, 1.25-9.59, P = 0.017); and UA groups (vs 20th to 80th percentile): < or =20th percentile, 2.98 (95% CI, 0.82-10.90, P = 0.099); > or = 80th percentile, 5.67 (95% CI, 1.71-18.78, P = 0.004). CONCLUSIONS: These preliminary observations suggest that HD patients in the lowest and highest quintiles of UA levels would face higher risk of mortality. Further studies with larger sample sizes will be needed to confirm these findings.     

Severity of renal vascular disease predicts mortality in patients undergoing coronary angiography

BACKGROUND: Renal artery stenosis (RAS) is a relatively uncommon but potentially reversible cause of renal failure. In a previous report, we demonstrated that the presence of RAS is independently associated with mortality in a group of patients undergoing coronary angiography. Our current study expands on this cohort, investigating the effect of the severity of RAS on all-cause mortality. METHODS: A total of 3987 patients underwent abdominal aortography immediately following coronary angiography. For the purpose of survival analysis, significant RAS was defined as > or =75% narrowing in the luminal diameter. RESULTS: Significant RAS was present in 4.8% of patients studied and was bilateral in 0.8%. Factors associated with the presence of RAS included female gender, older age, hypertension, congestive heart failure, elevated serum creatinine, and congestive heart failure. The four-year unadjusted survivals for patients with and without significant RAS were 57 and 89%, respectively (P < 0.001). Using the Cox proportional hazards model, the factors independently associated with decreased survival were the presence of RAS, increased age, the severity of coronary artery disease, the presence of comorbid disease, reduced ejection fraction, symptoms of congestive cardiac failure, and the mode of treatment of coronary artery disease. In the multivariate model, the presence of RAS conferred a hazard ratio of 2.01 (95% CI, 1.51 to 2.67, P < 0.001). We demonstrated an incremental effect on mortality according to the severity of RAS at baseline. Four-year adjusted survival for patients with 50%, 75%, and > or =95% stenosis was 70%, 68%, and 48%, respectively. In addition, bilateral disease was associated with four-year survival of 47% as compared with 59% for patients with unilateral disease (P < 0.001). The impact of RAS on survival remained robust regardless of the manner of treatment of coronary artery disease [that is, medical, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft (CABG)]. CONCLUSIONS: In this patient population, the presence of RAS is a strong independent predictor of mortality. Increasing severity of RAS has an incremental effect on survival probability.     

Predictors of reduced coronary flow reserve in heart transplant recipients without angiographically significant coronary artery disease

BACKGROUND: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography. METHODS: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR. RESULTS: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR. CONCLUSION: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.     

Serum uric acid and renal prognosis in patients with IgA nephropathy

BACKGROUND/AIMS: This study was designed to elucidate the clinical significance of serum uric acid (SUA) and the relationship between hyperuricemia and renal prognosis in IgA nephropathy. METHODS: The correlation between SUA and other clinical parameters were examined in 748 IgA nephropathy patients (432 males and 316 females). Among these patients, 226 (144 males and 82 females) who were followed for more than 5 years were examined for the relationship between hyperuricemia and renal prognosis. RESULTS: In IgA nephropathy, SUA correlated negatively with creatinine clearance (Ccr), and positively with urinary protein and tubulointerstitial damage. SUA was higher in patients with hypertension or diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p = 0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after more than 8 years was -22.3 +/- 20.8% in 13 patients with hyperuricemia, compared with +2.6 +/- 39.4% in 43 patients without hyperuricemia (p = 0.0238). Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461). CONCLUSION: Hyperuricemia in IgA nephropathy is derived from both glomerular and tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a risk factor for renal prognosis in IgA nephropathy.     

Serum alkaline phosphatase predicts mortality among maintenance hemodialysis patients

Several observational studies have demonstrated that serum levels of minerals and parathyroid hormone (PTH) have U- or J-shaped associations with mortality in maintenance hemodialysis patients, but the relationship between serum alkaline phosphatase (AlkPhos) and risk for all-cause or cardiovascular death is unknown. In this study, a 3-yr cohort of 73,960 hemodialysis patients in DaVita outpatient dialysis were studied, and the hazard ratios for all-cause and cardiovascular death were higher across 20-U/L increments of AlkPhos, including within the various strata of intact PTH and serum aspartate aminotransferase. In the fully adjusted model, which accounted for demographics, comorbidity, surrogates of malnutrition and inflammation, minerals, PTH, and aspartate aminotransferase, AlkPhos > or =120 U/L was associated with a hazard ratio for death of 1.25 (95% confidence interval 1.21 to 1.29; P < 0.001). This association remained among diverse subgroups of hemodialysis patients, including those positive for hepatitis C antibody. A rise in AlkPhos by 10 U/L during the first 6 mo was incrementally associated with increased risk for death during the subsequent 2.5 yr. In summary, high levels of serum AlkPhos, especially >120 U/L, are associated with mortality among hemodialysis patients. Prospective controlled trials will be necessary to test whether serum AlkPhos measurements could be used to improve the management of renal osteodystrophy.     

Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease

Background

Increased inflammation is common in patients with chronic kidney disease (CKD) and is associated with increased adverse cardiovascular events (CVE). Neutrophil-to-lymphocyte ratio (NLR) was used to predict survival in patients with acute coronary syndrome. We aimed to evaluate predictive ability of NLR in CKD patients.

Methods

225 subjects with stage 3–5 CKD were followed for a mean of 39 months. Fatal and nonfatal CVE were recorded during this period. NLR at baseline was determined from complete blood count differential. Endothelial dysfunction (flow-mediated dilation, FMD), hsCRP and insulin resistance were determined. We investigated if NLR could predict development of fatal and nonfatal CVE. We also looked at how NLR and its individual components change across CKD stages and whether NLR is related to CRP, insulin resistance and endothelial dysfunction.

Results

There were 70, 74 and 81 patients in groups of CKD stage-3, stage-4 and stage-5, respectively. Median NLR was 2.81. NLR showed a significant increase from stage 3 to stage 5. NLR was inversely associated with FMD independent of hsCRP. 14 fatal and 52 nonfatal CVE occurred during follow-up period. NLR could predict composite CVE independent of insulin resistance and hsCRP. Increased NLR over 2.81 was related to a significantly decreased survival time (log-rank Chi-square = 14.833, P < 0.0001). A cutoff value for NLR ≥3.76 could predict development of composite CVE with 80.3 % sensitivity and 91.8 % specificity.

Conclusions

NLR is independently related to endothelial dysfunction and could predict composite cardiovascular endpoints independent of traditional confounding factors in patients with moderate to severe CKD.     

Serum adiponectin predicts all-cause mortality and end stage renal disease in patients with type I diabetes and diabetic nephropathy

Adiponectin levels are increased in patients with type I diabetes especially in the presence of microangiopathy. Here we determined the predictive value of serum adiponectin levels and 8 adiponectin gene polymorphisms for mortality, cardiovascular events and end-stage renal disease in type I diabetic patients. This prospective, observational follow-up study of type I diabetics consisted of 438 patients with overt diabetic nephropathy that were compared to 440 type I patients with normal albumin excretion. These two groups were followed an average of 8 years and generally matched for gender, age and duration of diabetes. Cox regression analysis of 373 patients showed a covariate-adjusted hazard ratio for all-cause mortality of 1.46 for a change of one standard deviation in log10 of serum adiponectin. There was no association with cardiovascular events; however, serum adiponectin levels predicted end stage renal disease in a covariate-adjusted analysis. Two of eight gene polymorphisms, found in the 878 patients, were associated with increased serum adiponectin levels but none of the polymorphisms were associated with a renal or cardiovascular outcome. These studies show that high serum adiponectin levels predict mortality and progression to end stage renal disease in type I diabetic patients.     

Serum uric acid is associated with high blood pressure in pediatric hemodialysis patients

Serum uric acid (UA) is positively associated with hypertension (HTN). HTN is common in pediatric patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We assessed the relationship between UA and BP in 63 pediatric dialysis patients by measuring pre-treatment UA levels and BP in HD patients and in-center UA levels and blood pressure (BP) in PD patients. UA levels were similar in both groups [6.8 ± 0.2 (HD) vs. 6.5 ± 0.3 (PD), p = 0.6]. Pre-treatment systolic BP percentile was associated with a high UA level [91.9 ± 2.3 (>6.0 mg/dL) vs. 79.3 ± 5.8 mm Hg (≤6.0 mg/dL), p = 0.01] in HD patients only. There was a negative relationship between UA and dialysis vintage (r = −0.31, p = 0.01). In both groups, there was no relationship between UA and Kt/V. In HD patients, fluid overload was unrelated to UA level [4.2 ± 0.6% (≤6.0 mg/dL) vs. 4.3 ± 0.3% (>6.0 mg/dL), p = 0.9]. Moreover, pre-HD treatment systolic BP percentile correlated with UA (beta 0.36, p = 0.02) independent of volume. UA levels were higher in patients receiving anti-hypertensive medications [6.3 ± 0.2 (No Meds] vs 7.0 ± 0.2 (BP Meds) mg/dL,  p= 0.01]. Finally, there was no relationship between serum UA and normalized protein catabolic rate (r = 0.14; p = 0.4). In summary, serum UA impacts BP in pediatric HD patients, independent of volume, nutritional and weight status.     

Fibrinogen predicts mortality in high risk patients with peripheral artery disease.

OBJECTIVE: Fibrinogen plays a key role in the pathogenesis of atherosclerosis and complications of atherothrombotic disease. We investigated the prognostic impact of fibrinogen levels on mortality of high risk patients with peripheral artery disease (PAD). METHODS: We studied 486 patients with PAD and several cardiovascular comorbidities. Atherosclerotic risk factors and fibrinogen levels were determined at initial presentation and patients were followed for median 7 years (IQR 6-10) for all-cause and cardiovascular mortality. Multivariate Cox regression analysis was applied to assess the predictive value of fibrinogen levels (in quartiles) on patients' outcome. RESULTS: Cumulative survival rates at 1, 3, 5 and 10 years were 96, 91, 83 and 67%, respectively. Overall, 138 patients (28%) died, 70% of these patients died of cardiovascular complications (n=96). Patients with fibrinogen levels 10.2-12.2 micromol/l (third quartile) and patients with fibrinogen levels above 12.2 micromol/l (fourth quartile) had a significantly increased adjusted risk for all-cause mortality (hazard ratios [HR] 1.87 and 1.90, p=0.025 and p=0.020, respectively) compared to patients in the lowest quartile (fibrinogen below 8.6 micromol/l). A consistent effect was observed for cardiovascular causes of death. Diabetes mellitus and critical limb ischemia were the only other independent predictor variables (HR 2.08, p<0.001 and 1.88, p=0.001, respectively). CONCLUSION: Elevated fibrinogen levels in high risk patients with PAD indicate an increased risk for poor outcome, particularly for fatal cardiovascular complications.     

老年糖尿病肾病血尿酸浓度与冠心病相关性研究

目的 探讨糖尿病肾病老年患者的尿酸浓度与冠心病的相关性.方法 选取本院2012年2月～2014年2月收治的糖尿病肾病合并冠心病的老年患者165例作为观察组,同时选择83例单纯糖尿病肾病老年患者作为对照组,分别开展各项生化指标的检验,并进行比较与分析.结果 观察组患者的血肌酐水平为(96.7±20.1)mmol/L,血尿酸水平为(410.8 ±64.1) μmol/L,高密度脂蛋白胆固醇水平为(1.1±0.2) mmol/L,均与对照组具有显著差异(P＜0.05).观察组患者中男性与女性的血尿酸水平均与对照组有显著差异(P＜0.05).结论 老年糖尿病肾病患者的血尿酸浓度与冠心病发病存在较为密切的相关性,是冠心病的主要危险因素.临床通过对血尿酸水平开展相关检测,可准确预知心脑血管疾病的发生,并可通过检测结果来评估预后效果.     

尿酸联合脂蛋白a预测动脉粥样硬化高危人群肾动脉狭窄

目的 研究动脉粥样硬化高危人群中尿酸和脂蛋白a[Lp(a)]预测动脉粥样硬化性肾动脉狭窄( ARAS)的价值.方法 回顾性分析2008年10月至2011年4月在北京协和医院怀疑为ARAS,并接受肾动脉造影的190例患者的临床资料,其中89例诊为ARAS;部分患者同时接受了冠脉造影.对照组为年龄、性别匹配的180例同期本院常规体检人群.收集一般临床资料、血尿酸(UA)、Lp(a)、胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白( LDL)、Scr和C反应蛋白(CRP)等.分析ARAS患者的临床特点和相关危险因素,并利用二元Logistic回归分析尝试建立在高危人群中预测ARAS的临床决策工具.结果 ARAS患者的Scr、UA、Lp(a)和CRP水平显著地高于健康体检人群.高度怀疑ARAS或同时伴有冠状动脉病变而行肾动脉造影患者中,确诊ARAS组与非ARAS组生化指标、血脂、UA和肾功能差异均无统计学意义.二元Logistic回归分析显示,UA＞344μmol/L是ARAS发病的独立相关因素;且当UA＞344 μmol/L和Lp(a )＞242 mg/L时,预测ARAS的特异性达96％,阳性似然比为5.45,P=0.001,OR值为6.78,95％CI( 1.90～24.2),P=0.001.结论 ARAS的高危人群中,UA升高是ARAS的独立危险因素;UA联合Lp(a)对于预测ARAS有一定的临床意义.     

维持性血液透析患者血尿酸水平及其相关分析

目的通过对单中心维持性血液透析(maintenance hemodialysis,MHD)患者透析前血尿酸(serum uric acid,SUA)水平的横断面调查,分析透析人群中SUA的分布特点和影响因素,并探讨其临床意义。方法对海南省人民医院血液净化中心治疗的165例MHD患者进行透析前SUA、血肌酐、白蛋白及C反应蛋白等水平监测,研究高尿酸血症(hyperuricemia,HUA)的发生率及其影响因素。结果患者透析前平均SUA为(485±109)μmol/L,其中男性为(484±103)μmol/L,女性为(487±118)μmol/L,透析前男、女性平均SUA比较差异无统计学意义(P0.05)。HUA发生率为74.5%,其中男性为69.2%,女性为83.6%,男、女性HUA发生率比较差异有统计学意义(P0.05)。每周透析8 h及每周透析12 h的患者SUA比较差异无统计学意义[(493±102)μmol/L比(461±125)μmol/L,P0.05],2组HUA发生率比较差异无统计学意义(77%比67.4%,P0.05)。在年龄分组中SUA随年龄的增长呈先升后降趋势,其中40~50岁患者SUA最高。在原发病分组中,慢性肾炎组血尿酸水平高于糖尿病肾脏疾病组,差异有统计学意义[(503±102)μmol/L比(455±118)μmol/L,P0.017]。SUA与血红蛋白(r=0.223,P=0.004)、血磷(r=0.349,P0.0001)、血肌酐(r=0.490,P0.0001)呈正相关。结论 MHD患者透析前SUA高于正常人群,SUA水平不仅与肾脏功能减退有关,而且与透析患者的营养相关。SUA是反映MHD患者营养状态的指标之一。     

Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease

BACKGROUND: Prognosis in chronic obstructive pulmonary disease (COPD) is poorly predicted by indices of air flow obstruction, because other factors that reflect the systemic nature of the disease also influence prognosis. OBJECTIVE: To test the hypothesis that a reduction in quadriceps maximal voluntary contraction force (QMVC) is a useful predictor of mortality in patients with COPD. METHODS: A mortality questionnaire was sent to the primary care physician of 184 patients with COPD who had undergone quadriceps strength measurement over the past 5 years. QMVC was expressed as a percentage of the patient's body mass index. The end point measured was death or lung transplantation, and median (range) follow-up was 38 (1-54) months. RESULTS: Data were obtained for 162 patients (108 men and 54 women) with a mean (SD) percentage of forced expiratory volume in 1 s (FEV1) predicted of 35.6 (16.2), giving a response rate of 88%. Transplant-free survival of the cohort was 93.5% at 1 year and 87.1% at 2 years. Cox regression models showed that the mortality risk increased with increasing age and with reducing QMVC. Only age (HR 1.72 (95% CI 1.14 to 2.6); p = 0.01) and QMVC (HR 0.91 (95% CI 0.83 to 0.99); p = 0.036) continued to be significant predictors of mortality when controlled for other variables in the multivariate analysis. CONCLUSION: QMVC is simple and provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s.