Anders Danielsson

Comorbidity and Acute Clinical Events as Determinants of C-Reactive Protein Variation in Hemodialysis Patients: Implications for Patient Survival

BACKGROUND Patients with chronic kidney disease stage 5 have high comorbidity and are prone to inflammation that may contribute to the high cardiovascular mortality risk. STUDY DESIGN Three-month observational cohort study of prevalent hemodialysis patients. SETTINGS & PARTICIPANTS 228 hemodialysis patients (44% women) were included, median age of 66 years, median time on dialysis therapy of 29 months. PREDICTORS & OUTCOMES In part 1, comorbidity and intercurrent illness were predictors and C-reactive protein (CRP) level was the outcome. In part 2, serial CRP values were predictors and survival was the outcome. MEASUREMENTS High-sensitivity CRP was measured weekly and interleukin 6 (IL-6), tumor necrosis factor alpha, and IL-10 were measured monthly. Data for comorbidity were collected from patient records to calculate Davies comorbidity score, and self-reported clinical events were recorded weekly. RESULTS Median baseline CRP level was 6.7 mg/L (25th to 75th percentiles, 2.5 to 21 mg/L). Baseline CRP level correlated with time-averaged CRP (Spearman rho = 0.76) and individual median of serial CRP values (rho = 0.78; both P < 0.001). Part 1: comorbidity score was significantly associated with greater CRP and IL-6 levels. Age, sex, comorbidity, and 7 of 12 clinical events had significant effects on CRP level variation. Part 2: during a mean follow-up of 29 months, 38% of patients died. Median and mean serial CRP levels were associated with a greater hazard ratio for death (1.013; 95% confidence interval, 1.004 to 1.022) and 1.012 (95% confidence interval, 1.004 to 1.020) than baseline, maximum, and minimum CRP values during the study. Other significant covariates were age, Davies risk group, dialysis vintage, and albumin level. LIMITATIONS The study is based on observational data for prevalent dialysis patients. CONCLUSIONS Comorbidity and clinical events are strongly associated with inflammation in hemodialysis patients. Despite variability over time, inflammation assessed by using CRP level is a strong predictor of mortality. Serial measurements provide additional information compared with a single measurement.

Cardiovascular Function and Alveolar Gas Exchange during Isovolemic Hemodialysis with Acetate in Healthy Man

In order to elucidate the hemodynamic responses and alveolar gas exchange during isovolemic hemodialysis (IHD), without the influence of the uremic state and its complications, 7 healthy men underwent IHD. The dialysate contained acetate (40 mmol/l) and the sodium concentration was adjusted to the individuals predetermined plasma sodium concentration. By invasive techniques cardiac index (thermodilution), stroke index, heart rate, brachial and pulmonary arterial blood pressures, systemic vascular resistance index, central blood temperature, PaO2 and PaCO2 were measured. Calf vascular resistance was assessed by venous occlusion plethysmography. Plasma acetate was determined. A recirculation period of 30 min was followed by 120 min of IHD. During IHD plasma acetate increased to 2.51 +/- 0.30 mmol/l. Acetate provoked vascular dilatation, which was compensated for by a heart rate-dependent increase in cardiac index. Brachial arterial blood pressure and stroke index remained unchanged. PaCO2 and plasma bicarbonate decreased significantly, PaO2 tended to decrease and blood pH were unchanged. Thus, IHD with acetate in healthy man is mainly characterized by vasodilatation, but no cardiodepressive effects or marked hypoxemia. The adaptation to IHD is similar to that observed during treatment of uremic patients without complications.

Cardiovascular Function and Arterial Blood Gases during Sham Dialysis in Healthy Man

Cardiovascular function and alveolar gas exchange were studied in healthy subjects undergoing sham dialysis (SHD)--i.e. the circulation of blood through a cuprophane dialyzer with the dialysate compartment closed to avoid diffusion and convective transport of fluid and solutes. The blood-membrane contact induced complement activation (rise in C3d) and transient leukopenia, as described during clinical hemodialysis. PaO2, PaCO2 and calculated oxygen uptake remained unchanged. Heart rate, cardiac index (thermodilution), systemic vascular resistance index and brachial and pulmonary arterial blood pressures did not change significantly during 150 min of SHD (n = 8). In 12 subjects, in whom more frequent measurements were made during the first 30 min of SHD, pulmonary arterial systolic and diastolic blood pressures decreased significantly while the dialyzer and the tubing set filled with blood, and pulmonary arterial mean blood pressure did not change significantly. Pulmonary capillary wedge pressure fell during the filling phase, but did not change significantly during SHD; pulmonary vascular resistance index remained unchanged. We conclude that in nonuremic subjects sham dialysis with a cuprophane dialyzer does not result in hypoxemia, pulmonary vascular constriction and pulmonary hypertension, in spite of complement activation and marked leukopenia.

Cardiovascular Function and Arterial Blood Gases during Isolated Ultrafiltration in Healthy Man

In order to recognize possible cardiovascular signs of underhydration during isolated ultrafiltration (IUF), we have studied the physiological hemodynamic adaptation to IUF in healthy man both above and below normohydration. In 7 subjects IUF was performed with the subjects in a normohydrated state at the start of IUF. In 8 subjects the IUF was preceded by a 1-hour infusion of Ringer solution equal to 3% of body weight. By invasive techniques, cardiac index (thermodilution), stroke index, heart rate, brachial and pulmonary arterial blood pressures, systemic vascular resistance index, central blood temperature, PaO2 and PaCO2 were measured. Calf vascular resistance was assessed by venous occlusion plethysmography. A recirculation period of 30 min was followed by IUF in both study groups. During IUF with overhydration and normohydration at the start of IUF, cardiac output fell because of a decline in stroke volume and an unchanged heart rate. Blood pressure remained constant because of systemic vascular constriction. PaO2 and PaCO2 remained unchanged. IUF in healthy man is mainly characterized by vascular constriction and an unchanged heart rate. Thus, the cardiovascular adaptation to ultrafiltration was the same whether or not ultrafiltration was performed at overhydration or normohydration at the start of ultrafiltration. Therefore, it is unlikely that monitoring of heart rate or noninvasive recording of blood pressure can predict whether a subject is becoming underhydrated during isolated ultrafiltration. The adaptation to IUF is similar to that observed during the treatment of uremic patients without complications.