Siu-Fai Lui

Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study.

Calcification complications are frequent among long-term dialysis patients. However, the prognostic implication of cardiac valve calcification in this population is not known. This study aimed to determine if cardiac valve calcification predicts mortality in long-term dialysis patients. Baseline echocardiography was performed in 192 patients (mean +/- SD age, 55 +/- 12 yr) on continuous ambulatory peritoneal dialysis (mean +/- SD duration of dialysis, 39 +/- 31 mo) to screen for calcification of the aortic valve, mitral valve, or both. Valvular calcification was present in 62 patients. During the mean follow-up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes) were observed. Overall 1-yr survival was 70% and 93% for patients with and without valvular calcification (P < 0.0001, log-rank test). Cardiovascular mortality was 22% and 3% for patients with and without valvular calcification (P < 0.0001). Multivariable Cox regression analysis showed that cardiac valve calcification was predictive of an increased all-cause mortality (hazard ratio [HR], 2.50; 95% CI, 1.32 to 4.76; P = 0.005) and cardiovascular death (HR 5.39; 95% CI, 2.16 to 13.48; P = 0.0003) independent of age, male gender, dialysis duration, C-reactive protein, diabetes, and atherosclerotic vascular disease. Eighty-nine percent of patients with both valvular calcification and atherosclerotic vascular disease, 23% of patients with valvular calcification only, 21% of patients with atherosclerotic vascular disease only, and 13% of patients with neither complication died at 1-yr (P < 0.0005). The cardiovascular death rate was 85% for patients with both complications, 13% for patients with valvular calcification only, 14% for patients with atherosclerotic vascular disease only, and 5% for those with neither complication (P < 0.0005). The number of calcified valves was associated with all-cause mortality (P < 0.0005) and cardiovascular death (P < 0.0005). One-year all-cause mortality was 57% for patients with both aortic and mitral valves calcified, 40% for those with either valve calcified, and 15% for those with neither valve calcified. In conclusion, cardiac valve calcification is a powerful predictor for mortality and cardiovascular deaths in long-term dialysis patients. Valvular calcification by itself has similar prognostic importance as the presence of atherosclerotic vascular disease. Its coexistence with other atherosclerotic complications indicates more severe disease and has the worst outcome.

Inflammation, Residual Kidney Function, and Cardiac Hypertrophy Are Interrelated and Combine Adversely to Enhance Mortality and Cardiovascular Death Risk of Peritoneal Dialysis Patients

C-reactive protein (CRP), the prototype marker of inflammation, and cardiac hypertrophy are important prognostic indicators in dialysis patients. Residual renal function (RRF) has also been shown to influence survival of peritoneal dialysis (PD) patients. This study examined the relations between inflammation, RRF, and left ventricular hypertrophy (LVH) and determined whether inflammation, RRF, and LVH combine adversely to predict the outcomes of PD patients. A prospective observational study was performed in 231 chronic PD patients. Left ventricular mass index (LVMi), residual glomerular filtration rate (GFR), CRP, hemoglobin, serum albumin, and BP were determined at study baseline and related to outcomes. On univariate analysis, age (P = 0.002), dialysis duration (P = 0.004), coronary artery disease (P < 0.001), pulse pressure (P < 0.001), hemoglobin (P < 0.001), serum albumin (P = 0.032), log-CRP (P < 0.001), and GFR (P < 0.001) were significantly associated with log-LVMi. Log-CRP was positively correlated with pulse pressure (R = 0.218, P = 0.001) and negatively correlated with GFR (R = -0.272, P < 0.001). Multivariate analysis showed that log-CRP (P = 0.008) and RRF (P = 0.003) remained associated with log-LVMi independent of hemoglobin, serum albumin, arterial pulse pressure, and coronary artery disease. After follow-up for 30 +/- 14 mo, 34.2% patients had died. CRP, RRF, and LVMi each were significantly predictive of all-cause mortality and cardiovascular death. Kaplan-Meier analysis showed a significant increase in all-cause (P < 0.0001) and cardiovascular mortality (P < 0.0001) as the number of risk factors, namely CRP >/=50th percentile, no RRF, and LVMi>/= 50th percentile increased with the 2-yr all-cause mortality and cardiovascular death reaching as high as 61% and 46%, respectively, for patients who had all three risk factors. Compared with patients with none of the three risk factors, those with all three risk factors had an adjusted hazards ratio of 6.94 (P < 0.001) and 5.43 (P = 0.001) for all-cause mortality and cardiovascular mortality, respectively. In conclusion, inflammation, RRF, and LVH are interrelated and combine adversely to increase mortality and cardiovascular death risk of PD patients.

Is a Single Time Point C-Reactive Protein Predictive of Outcome in Peritoneal Dialysis Patients?

C-reactive protein is the prototype marker of inflammation and has been shown to predict mortality in hemodialysis patients. However, it remains uncertain as to whether a single C-reactive protein level has similar prognostic significance in peritoneal dialysis patients. A single high-sensitivity C-reactive protein (hs-CRP) level was measured in 246 continuous ambulatory peritoneal dialysis patients without active infections at study baseline together with indices of dialysis adequacy, echocardiographic parameters (left ventricular mass index, left ventricular dimensions, and ejection fraction), nutrition markers (serum albumin, dietary intake, and subjective global assessment) and biochemical parameters (hemoglobin, lipids, calcium, and phosphate). The cohort was then followed-up prospectively for a median of 24 mo (range, 2 to 34 mo), and outcomes were studied in relation to these parameters. Fifty-nine patients died (36 from cardiovascular causes) during the follow-up period. The median hs-CRP level was 2.84 mg/L (range, 0.20 to 94.24 mg/L). Patients were stratified into tertiles according to baseline hs-CRP, namely those with hs-CRP < or = 1.26 mg/L, 1.27 to 5.54 mg/L, and > or = 5.55 mg/L. Those with higher hs-CRP were significantly older (P < 0.001), had greater body mass index (P < 0.001), higher prevalence of coronary artery disease (P = 0.003), and greater left ventricular mass index (P < 0.001). One-year overall mortality was 3.9% (lower) versus 8.8% (middle) versus 21.3% (upper tertile) (P < 0.0001). Cardiovascular death rate was 2.7% (lower) versus 5.2% (middle) versus 16.2% (upper tertile) (P < 0.0001). Multivariable Cox regression analysis showed that every 1 mg/L increase in hs-CRP was independently predictive of higher all-cause mortality (hazard ratio [HR], 1.02; 95% CI, 1.01 to 1.04; P = 0.002) and cardiovascular mortality (HR, 1.03; 95% CI, 1.01 to 1.05; P = 0.001) in peritoneal dialysis patients. Other significant predictors for all-cause mortality included age (HR, 1.07; 95% CI, 1.04 to 1.10), gender (HR, 0.49; 95% CI, 0.27 to 0.90), atherosclerotic vascular disease (HR, 2.65; 95% CI, 1.46 to 4.80), left ventricular mass index (HR, 1.01; 95% CI, 1.00 to 1.01) and residual GFR (HR, 0.53; 95% CI, 0.38 to 0.75). Age (HR, 1.06; 95% CI, 1.02 to 1.10), history of heart failure (HR, 3.31; 95% CI, 1.36 to 8.08), atherosclerotic vascular disease (HR, 3.20; 95% CI, 1.43 to 7.13), and residual GFR (HR, 0.57; 95% CI, 0.38 to 0.86) were also independently predictive of cardiovascular mortality. In conclusion, a single, random hs-CRP level has significant and independent prognostic value in PD patients.

The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria

PURPOSE To determine the natural history of immunoglobulin (Ig) A nephropathy among patients who presented with hematuria and minimal proteinuria, and factors associated with the development of adverse clinical events, such as proteinuria. SUBJECTS AND METHODS In Hong Kong, all patients who present with isolated hematuria are referred for renal biopsy after urologic diseases are ruled out. We reviewed the clinical course of 72 consecutive patients with histologically confirmed IgA nephropathy who presented with hematuria and minimal proteinuria (0.4 g/day or less). All patients were normotensive and had normal renal function at presentation. Adverse events were defined as proteinuria greater than 1 g per day, hypertension, or impaired renal function (serum creatinine level 120 micromol/L or estimated creatinine clearance < 70 mL per minute). RESULTS The mean (+/- SD) age at presentation was 27 +/- 8 years; 56 (78%) were female. Nine patients (13%) had grade 2 histologic lesions. During a median follow-up of 7 years, 32 patients (44%) developed adverse events: 24 (33%) developed proteinuria of 1 g per day or more, 19 (26%) became hypertensive, and 5 (7%) developed impaired renal function. Another 30 patients (42%) had persistently abnormal urinalysis examinations. Only 10 patients (14%) had complete resolution of hematuria. The median time for progression from proteinuria (> l g/day) to renal impairment was 84 months (range 56 to 132). In a multivariate analysis, age at presentation (relative risk [RR] per 10 years of age = 2.0; 95% confidence interval [CI], 1.2 to 3.4) and histologic grade (grade 2 versus grade 1, RR = 4.5; 95% CI, 1.7 to 12) were independent predictors of developing an adverse event. CONCLUSIONS IgA nephropathy that presents with hematuria and minimal proteinuria is usually a progressive disease. Life-long follow-up with regular monitoring of blood pressure and proteinuria is recommended.

N-Terminal Pro-Brain Natriuretic Peptide: An Independent Risk Predictor of Cardiovascular Congestion, Mortality, and Adverse Cardiovascular Outcomes in Chronic Peritoneal Dialysis Patients

This study was performed to determine whether the N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is a useful biomarker in predicting cardiovascular congestion, mortality, and cardiovascular death and event in chronic peritoneal dialysis (PD) patients. A prospective cohort study was conducted in 230 chronic PD patients in a dialysis unit of a university teaching hospital. Serum NT-pro-BNP was measured at baseline together with echocardiography and dialysis indices. Each patient was followed for 3 yr from the day of enrollment or until death. Time to develop first episode of cardiovascular congestion and other cardiovascular event and time to mortality and cardiovascular death were studied in relation to NT-pro-BNP. NT-pro-BNP showed the strongest correlation with residual GFR, followed by left ventricular ejection fraction and left ventricular mass index. In the univariate Cox regression model, NT-pro-BNP was a significant predictor of cardiovascular congestion, mortality, and cardiovascular death and event. In the fully adjusted multivariable Cox regression analysis that included residual GFR, left ventricular ejection fraction, and left ventricular mass index, the hazard ratios for cardiovascular congestion, mortality, composite end point of mortality and cardiovascular congestion, and cardiovascular death and event for patients of the fourth quartile were 4.25 (95% confidence interval [CI] 1.56 to 11.62; P = 0.005), 4.97 (95% CI 1.35 to 18.28; P = 0.016), 5.03 (95% CI 2.07 to 12.26; P < 0.001), 7.50 (95% CI 1.36 to 41.39; P = 0.021), and 9.10 (95% CI 2.46 to 33.67; P = 0.001), respectively, compared with the first quartile. These data showed that NT-pro-BNP is an important risk predictor of cardiovascular congestion, mortality, and adverse cardiovascular outcomes in chronic PD patients and adds important prognostic information beyond that contributed by left ventricular hypertrophy, systolic dysfunction, and other conventional risk factors.

Sudden Cardiac Death in End-Stage Renal Disease Patients: A 5-Year Prospective Analysis

Abstract—End-stage renal disease patients experience a high incidence of sudden cardiac death. We performed a 5-year prospective study in 230 end-stage renal disease patients, aiming to determine the role of echocardiography and the additional value of serum biomarkers in predicting sudden cardiac death. During follow-up, 24% of all deaths were attributed to sudden cardiac death. In the multivariable Cox regression analysis considering clinical, biochemical, dialysis, and echocardiographic parameters, left ventricular systolic dysfunction emerged as the most significant predictor of sudden cardiac death, followed by a high systolic and a low diastolic blood pressure. An ejection fraction cutoff ≤48.0% is associated with a specificity of 78.6% and a sensitivity of 57.7% in predicting sudden cardiac death. In biomarker-based multivariable Cox regression analysis, N-terminal probrain natriuretic peptide displays an independent association with sudden cardiac death and is more significantly associated with sudden cardiac death than cardiac troponin T. In the combined echocardiography and biomarker-based multivariable Cox regression model, N-terminal probrain natriuretic peptide loses significance to left ventricular ejection fraction, whereas cardiac troponin T retains a significant association with sudden cardiac death independent of echocardiographic parameters. In conclusion, systolic dysfunction is the most significant predictor of sudden cardiac death followed by a high systolic and a low diastolic blood pressure. Our data suggest additional value in measuring cardiac troponin T for sudden cardiac death risk stratification. N-terminal probrain natriuretic peptide may be used in place of echocardiography to identify patients at risk of sudden cardiac death but had no added value over echocardiography in predicting sudden cardiac death.

Diagnostic potential of serum biomarkers for left ventricular abnormalities in chronic peritoneal dialysis patients

BACKGROUND N-terminal-pro-brain natriuretic peptide, cardiac troponin T (cTnT) and high sensitivity C-reactive protein (hs-CRP) have been shown to predict mortality and cardiovascular outcomes in end-stage renal disease patients. However, it is not known which biomarkers have the strongest diagnostic potential for left ventricular (LV) abnormalities in chronic peritoneal dialysis (PD) patients, nor whether residual renal function may confound the diagnostic potential of these biomarkers. METHODS Two hundred and thirty chronic PD patients underwent two-dimensional echocardiography to determine LV hypertrophy and ejection fraction and had simultaneous measurement of serum NT-pro-BNP, cTnT and hs-CRP. RESULTS A significant gain in predictive power was observed when NT-pro-BNP or cTnT but not hs-CRP was included in the multivariable logistic regression models for severe LV hypertrophy (defined as LV mass index > or = upper tertile, 247.8 g/m(2)) and systolic dysfunction (defined as ejection fraction < or =45%). Using ROC curve analysis, NT-pro-BNP had the highest diagnostic value for severe LV hypertrophy and systolic dysfunction compared to cTnT and hs-CRP, irrespective of residual renal function. An analysis based on the best cut-off threshold showed that NT-pro-BNP and cTnT had a negative predictive value of 87.1% and 92.6% for severe LV hypertrophy and 95.4% and 93.2% for systolic dysfunction, respectively. Furthermore, the best cut-off threshold of NT-pro-BNP and cTnT for excluding severe LV hypertrophy and systolic dysfunction was nearly 3-fold higher in anuric patients than in patients with residual renal function. CONCLUSIONS Serum NT-pro-BNP appeared most useful in excluding systolic dysfunction in chronic PD patients followed by cTnT. hs-CRP was not useful in this regard. Residual renal function confounded the interpretation of these biomarkers and reduced their predictive power. A nearly 30% higher cut-off threshold of NT-pro-BNP and cTnT had to be applied in anuric PD patients.

Long-term mortality and cardiovascular risk stratification of peritoneal dialysis patients using a combination of inflammation and calcification markers

BACKGROUND It remains unknown whether a composite of inflammation and calcification markers provides better mortality and cardiovascular risk stratification in chronic peritoneal dialysis (PD) patients. METHODS We performed a 4-year prospective follow-up study in 231 chronic PD patients from a single regional dialysis centre in Hong Kong. Valvular calcification was detected using echocardiography, and fasting venous blood was collected to measure a panel of inflammation markers. The patients were stratified into five groups on the basis of 0, 1, 2, 3 and all 4 inflammation and calcification risk markers, namely high C-reactive protein (CRP) (CRP in upper tertile), high interleukin-6 (IL-6) (IL-6 in upper tertile), low fetuin-A (fetuin-A in lower tertile) and valvular calcification. Study outcomes included all-cause and cardiovascular mortality and fatal or non-fatal cardiovascular events (CVEs). RESULTS The patients with 4, 3, 2 and 1 markers had an adjusted hazard ratio (HR) of 5.17 (95% CI, 1.81-14.77, P = 0.002), 3.38 (95% CI, 1.50-7.60; P = 0.003), 2.17 (95% CI, 0.98-4.77; P = 0.056) and 2.42 (95% CI, 1.18-4.96; P = 0.016), respectively, for mortality at 4 years than those with 0 risk marker. The adjusted HRs for fatal or non-fatal CVEs were 4.33 (95% CI, 1.70-11.03; P = 0.002), 1.60 (95% CI, 0.73-3.52; P = 0.24), 1.92 (95% CI, 0.95-3.90; P = 0.07) and 1.33 (95% CI, 0.67-2.62; P = 0.42), respectively, for patients with 4, 3, 2 and 1 markers than those with 0 risk markers. CONCLUSIONS A composite of inflammation and calcification markers provides long-term prognostication and identifies the sickest PD patients with the worst clinical outcomes. Since these parameters can all be obtained quite readily, our data support the adoption of a multiinflammation and calcification risk marker approach for mortality and cardiovascular risk stratification in PD patients.

Is Valvular Calcification a Part of the Missing Link between Residual Kidney Function and Cardiac Hypertrophy in Peritoneal Dialysis Patients

BACKGROUND AND OBJECTIVES Residual renal function (RRF) predicts survival and shows an important inverse relation with cardiac hypertrophy in peritoneal dialysis (PD) patients. We hypothesized that valvular calcification and the calcification milieu may be part of the process linking loss of RRF and cardiac hypertrophy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cross-sectional study was conducted by performing two-dimensional echocardiography on 230 PD patients to assess valvular calcification and left ventricular (LV) mass and collecting 24-h urine for estimation of RRF. RESULTS Patients having valvular calcification had lower RRF than those without. Patients with no RRF showed higher calcium-phosphorus product (Ca x P) and C-reactive protein (CRP). Using multiple logistic regression analysis, every 1-ml/min per 1.73 m(2) increase in residual GFR was associated with a 28% reduction in the risk for valvular calcification. The association was lost after additional adjustment for Ca x P and CRP. Using multiple linear regression analysis, loss of RRF showed significant association with increased LV mass index, but this association was lost after additional adjustment for CRP, Ca x P, and valvular calcification. Patients with all three calcification risk factors, namely inflammation, high CaxP, and no RRF, showed the highest prevalence of valvular calcification and had the most severe cardiac hypertrophy. CONCLUSIONS The association among loss of RRF, valvular calcification, and cardiac hypertrophy was closely linked to increased inflammation and high Ca x P in PD patients. These data suggest that valvular calcification and the calcification milieu are part of the processes linking loss of RRF and worsening cardiac hypertrophy in PD.

Prognostic Value of Plasma Myeloperoxidase in ESRD Patients

BACKGROUND Myeloperoxidase (MPO) has been suggested to have a role in atherosclerosis through its strong oxidative capacity. We hypothesized that MPO level may predict clinical outcomes in patients with end-stage renal disease receiving long-term peritoneal dialysis (PD) therapy. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 236 long-term PD patients were recruited from a single regional dialysis unit in Hong Kong between April 1999 and February 2001. PREDICTOR Level of plasma MPO, analyzed using a sandwich enzyme-linked immunosorbent assay. OUTCOME & MEASUREMENT Mortality and fatal or nonfatal cardiovascular events at 3 years. RESULTS The distribution of MPO levels was skewed with a median of 31.8 μg/L (25th-75th percentiles, 24.4-42.7). There were 69 deaths and 81 cardiovascular events. Adjusting for traditional and nontraditional risk factors and C-reactive protein, cardiac troponin T, and N-terminal pro-brain natriuretic peptide levels, a doubling in plasma MPO level was associated independently with a 46% (95% CI, 1.02-2.08; P = 0.04) and 60% (95% CI, 1.17-2.18; P = 0.003) increase in risks of mortality and cardiovascular events, respectively. Log(2)MPO showed significant additional predictive value for mortality (P = 0.04) and cardiovascular events (P = 0.005) when included in Cox regression models consisting of clinical, demographic, dialysis, echocardiographic, and biochemical parameters, as well as C-reactive protein, cardiac troponin T, and N-terminal pro-brain natriuretic peptide levels. LIMITATIONS MPO was measured at a single time and did not reflect changes over time. CONCLUSIONS These data suggest that plasma MPO level has significant independent and additional prognostic value beyond the standard clinical, biochemical, and echocardiographic parameters and is useful for outcome stratification in long-term PD patients. MPO may be an important mediator of increased cardiovascular risk in patients with end-stage renal disease and warrants further investigation.