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1.  Factors associated with 24-hour urinary volume: the Swiss salt survey 
BMC Nephrology  2013;14:246.
Background
Low 24-hour urine volume (24UV) may be a significant risk factor for decline in kidney function. We therefore aimed to study associated markers and possible determinants of 24UV in a sample of the Swiss population.
Methods
The cross-sectional Swiss Salt Study included a population-based sample of 1535 (746 men and 789 women) individuals from three linguistic regions of Switzerland. Data from 1300 subjects were available for the present analysis. 24UV was measured using 24-hour urine collection. Determinants of 24UV were identified using multivariable linear regression models.
Results
In bivariate analysis, 24UV was higher in women compared to men (2000 ml/24 h [interquartile range (IQR): 1354, 2562] versus 1780 ml/24 h [IQR: 1244, 2360], p = 0.002). In multivariable regression analyses, independent associated markers of 24UV were female sex (β = 280, 95% confidence interval [CI]: 174, 386, p < 0.0001), fluid intake (β = 604, 95% CI: 539, 670, p < 0.0001), sodium excretion (β = 4.2, 95% CI: 3.4, 4.9, p < 0.0001) age (β = 6.6, CI: 3.4, 9.7, p < .0001), creatinine clearance (β = 2.4, CI: 0.2, 4.6, p = 0.04), living in the German-speaking part of Switzerland (β = 124, CI: 29, 219, p = 0.01), alcohol consumption (β = 41, CI: 9, 73, p = 0.01 for increasing categories of alcohol consumption), body mass index (β = −32, CI: -45, -18, p < 0.0001), current smoking (β = −146, CI: -265, -26, p = 0.02), and consumption of meat and cold cut (β = −56, CI: -108, -5, p = 0.03).
Conclusion
In this large population-based, cross-sectional study, we found several strong and independent correlates for 24UV. These findings may be important to improve our understanding in the development of chronic kidney disease.
doi:10.1186/1471-2369-14-246
PMCID: PMC4226251  PMID: 24199987
Daily urinary volume; Kidney function; Prevention; Population based study; Salt; Gender; Salt excretion
2.  Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial 
BMC Nephrology  2013;14:157.
Background
In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients.
Methods
The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2 years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference.
Results
No difference was found in the mean values of biological parameters (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but resulted in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability. Q2W administration interval was however more favorable in terms of ESAs dose, allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa.
Conclusions
The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy. The ESAs administration interval had a greater impact on hemoglobin variability than the ESAs type. The more protracted reticulocyte response induced by C.E.R.A. could explain both, the observed higher risk of overshoot and the significant increase in efficacy when shortening its administration interval.
Trial registration
ClinicalTrials.gov: NCT01666301
doi:10.1186/1471-2369-14-157
PMCID: PMC3733800  PMID: 23870287
Erythropoietin stimulating agents; Hemoglobin; Reticulocytes; Variability
3.  Haemodynamic consequences of changing potassium concentrations in haemodialysis fluids 
BMC Nephrology  2011;12:14.
Background
A rapid decrease of serum potassium concentrations during haemodialysis produces a significant increase in blood pressure parameters at the end of the session, even if effects on intra-dialysis pressure are not seen. Paradoxically, in animal models potassium is a vasodilator and decreases myocardial contractility. The purpose of this trial is to study the precise haemodynamic consequences induced by acute changes in potassium concentration during haemodialysis.
Methods
In 24 patients, 288 dialysis sessions, using a randomised single blind crossover design, we compared six dialysate sequences with different potassium profiles. The dialysis sessions were divided into 3 tertiles, casually modulating potassium concentration in the dialysate between the value normally used K and the two cut-off points K+1 and K-1 mmol/l. Haemodynamics were evaluated in a non-invasive manner using a finger beat-to-beat monitor.
Results
Comparing K-1 and K+1, differences were found within the tertiles regarding systolic (+5.3, +6.6, +2.3 mmHg, p < 0.05, < 0.05, ns) and mean blood pressure (+4.3, +6.4, -0.5 mmHg, p < 0.01, < 0.01, ns), as well as peripheral resistance (+212, +253, -4 dyne.sec.cm-5, p < 0.05, < 0.05, ns). The stroke volume showed a non-statistically-significant inverse trend (-3.1, -5.2, -0.2 ml). 18 hypotension episodes were recorded during the course of the study. 72% with K-1, 11% with K and 17% with K+1 (p < 0.01 for comparison K-1 vs. K and K-1 vs. K+1).
Conclusions
A rapid decrease in the concentration of serum potassium during the initial stage of the dialysis-obtained by reducing the concentration of potassium in the dialysate-translated into a decrease of systolic and mean blood pressure mediated by a decrease in peripheral resistance. The risk of intra-dialysis hypotension inversely correlates to the potassium concentration in the dialysate.
Trial Registration Number
NCT01224314
doi:10.1186/1471-2369-12-14
PMCID: PMC3079606  PMID: 21470404
Haemodynamics; hypotension; potassium; haemodialysis; dialysis fluids
4.  Development of an erythropoietin prescription simulator to improve abilities for the prescription of erythropoietin stimulating agents: Is it feasible? 
BMC Nephrology  2011;12:11.
Background
The increasing use of erythropoietins with long half-lives and the tendency to lengthen the administration interval to monthly injections call for raising awareness on the pharmacokinetics and risks of new erythropoietin stimulating agents (ESA). Their pharmacodynamic complexity and individual variability limit the possibility of attaining comprehensive clinical experience. In order to help physicians acquiring prescription abilities, we have built a prescription computer model to be used both as a simulator and education tool.
Methods
The pharmacokinetic computer model was developed using Visual Basic on Excel and tested with 3 different ESA half-lives (24, 48 and 138 hours) and 2 administration intervals (weekly vs. monthly). Two groups of 25 nephrologists were exposed to the six randomised combinations of half-life and administration interval. They were asked to achieve and maintain, as precisely as possible, the haemoglobin target of 11-12 g/dL in a simulated naïve patient. Each simulation was repeated twice, with or without randomly generated bleeding episodes.
Results
The simulation using an ESA with a half-life of 138 hours, administered monthly, compared to the other combinations of half-lives and administration intervals, showed an overshooting tendency (percentages of Hb values > 13 g/dL 15.8 ± 18.3 vs. 6.9 ± 12.2; P < 0.01), which was quickly corrected with experience. The prescription ability appeared to be optimal with a 24 hour half-life and weekly administration (ability score indexing values in the target 1.52 ± 0.70 vs. 1.24 ± 0.37; P < 0.05). The monthly prescription interval, as suggested in the literature, was accompanied by less therapeutic adjustments (4.9 ± 2.2 vs. 8.2 ± 4.9; P < 0.001); a direct correlation between haemoglobin variability and number of therapy modifications was found (P < 0.01).
Conclusions
Computer-based simulations can be a useful tool for improving ESA prescription abilities among nephrologists by raising awareness about the pharmacokinetic characteristics of the various ESAs and recognizing the factors that influence haemoglobin variability.
doi:10.1186/1471-2369-12-11
PMCID: PMC3055807  PMID: 21332992
5.  Anemia and chronic kidney disease are potential risk factors for mortality in stroke patients: a historic cohort study 
BMC Nephrology  2010;11:27.
Background
Chronic kidney disease (CKD) is associated to a higher stroke risk. Anemia is a common consequence of CKD, and is also a possible risk factor for cerebrovascular diseases. The purpose of this study was to examine if anemia and CKD are independent risk factors for mortality after stroke.
Methods
This historic cohort study was based on a stroke registry and included patients treated for a first clinical stroke in the stroke unit of one academic hospital over a three-year period. Mortality predictors comprised demographic characteristics, CKD, glomerular filtration rate (GFR), anemia and other stroke risk factors. GFR was estimated by means of the simplified Modification of Diet in Renal Disease formula. Renal function was assessed according to the Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD classification in five groups. A value of hemoglobin < 120 g/L in women and < 130 g/L in men on admission defined anemia. Kaplan-Meier survival curves and Cox models were used to describe and analyze one-year survival.
Results
Among 890 adult stroke patients, the mean (Standard Deviation) calculated GFR was 64.3 (17.8) ml/min/1.73 m2 and 17% had anemia. Eighty-two (10%) patients died during the first year after discharge. Among those, 50 (61%) had K/DOQI CKD stages 3 to 5 and 32 (39%) stages 1 or 2 (p < 0.001). Anemia was associated with an increased risk of death one year after discharge (p < 0.001). After adjustment for other factors, a higher hemoglobin level was independently associated with decreased mortality one year after discharge [hazard ratio (95% CI) 0.98 (0.97-1.00)].
Conclusions
Both CKD and anemia are frequent among stroke patients and are potential risk factors for decreased one-year survival. The inclusion of patients with a first-ever clinical stroke only and the determination of anemia based on one single measure, on admission, constitute limitations to the external validity. We should investigate if an early detection and management of both CKD and anemia could improve survival in stroke patients.
doi:10.1186/1471-2369-11-27
PMCID: PMC2973927  PMID: 20950484
6.  Citrate- vs. acetate-based dialysate in bicarbonate haemodialysis: consequences on haemodynamics, coagulation, acid-base status, and electrolytes 
BMC Nephrology  2009;10:7.
Background
A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency.
Methods
In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers.
Results
Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate.
Conclusion
The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.
Trial registration
ClinicalTrials.gov NCT00718289
doi:10.1186/1471-2369-10-7
PMCID: PMC2657128  PMID: 19265544
7.  Optimal and continuous anaemia control in a cohort of dialysis patients in Switzerland 
BMC Nephrology  2008;9:16.
Background
Guidelines for the management of anaemia in patients with chronic kidney disease (CKD) recommend a minimal haemoglobin (Hb) target of 11 g/dL. Recent surveys indicate that this requirement is not met in many patients in Europe. In most studies, Hb is only assessed over a short-term period. The aim of this study was to examine the control of anaemia over a continuous long-term period in Switzerland.
Methods
A prospective multi-centre observational study was conducted in dialysed patients treated with recombinant human epoetin (EPO) beta, over a one-year follow-up period, with monthly assessments of anaemia parameters.
Results
Three hundred and fifty patients from 27 centres, representing 14% of the dialysis population in Switzerland, were included. Mean Hb was 11.9 ± 1.0 g/dL, and remained stable over time. Eighty-five % of the patients achieved mean Hb ≥ 11 g/dL. Mean EPO dose was 155 ± 118 IU/kg/week, being delivered mostly by subcutaneous route (64–71%). Mean serum ferritin and transferrin saturation were 435 ± 253 μg/L and 30 ± 11%, respectively. At month 12, adequate iron stores were found in 72.5% of patients, whereas absolute and functional iron deficiencies were observed in only 5.1% and 17.8%, respectively. Multivariate analysis showed that diabetes unexpectedly influenced Hb towards higher levels (12.1 ± 0.9 g/dL; p = 0.02). One year survival was significantly higher in patients with Hb ≥ 11 g/dL than in those with Hb <11 g/dL (19.7% vs 7.3%, p = 0.006).
Conclusion
In comparison to European studies of reference, this survey shows a remarkable and continuous control of anaemia in Swiss dialysis centres. These results were reached through moderately high EPO doses, mostly given subcutaneously, and careful iron therapy management.
doi:10.1186/1471-2369-9-16
PMCID: PMC2621153  PMID: 19077225
8.  Would artificial neural networks implemented in clinical wards help nephrologists in predicting epoetin responsiveness? 
BMC Nephrology  2006;7:13.
Background
Due to its strong intra- and inter-individual variability, predicting the ideal erythropoietin dose is a difficult task. The aim of this study was to re-evaluate the impact of the main parameters known to influence the responsiveness to epoetin beta and to test the performance of artificial neural networks (ANNs) in predicting the dose required to reach the haemoglobin target and the monthly dose adjustments.
Methods
We did a secondary analysis of the survey on Anaemia Management in dialysis patients in Switzerland; a prospective, non-randomized observational study, enrolling 340 patients of 26 centres and in order to have additional information about erythropoietin responsiveness, we included a further 92 patients from the Renal Services of the Ente Ospedaliero Cantonale, Bellinzona, Switzerland. The performance of ANNs in predicting the epoetin dose was compared with that of linear regressions and of nephrologists in charge of the patients.
Results
For a specificity of 50%, the sensitivity of ANNs compared with linear regressions in predicting the erythropoietin dose to reach the haemoglobin target was 78 vs. 44% (P < 0.001). The ANN built to predict the monthly adaptations in erythropoietin dose, compared with the nephrologists' opinion, allowed to detect 48 vs. 25% (P < 0.05) of the patients treated with an insufficient dose with a specificity of 92 vs. 83% (P < 0.05).
Conclusion
In predicting the erythropoietin dose required for an individual patient and the monthly dose adjustments ANNs are superior to nephrologists' opinion. Thus, ANN may be a useful and promising tool that could be implemented in clinical wards to help nephrologists in prescribing erythropoietin.
doi:10.1186/1471-2369-7-13
PMCID: PMC1578551  PMID: 16981983
9.  Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients 
BMC Nephrology  2006;7:3.
Background
Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission.
Methods
We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine ≥ 124 956;mol/L for women and ≥ 133 μmol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions.
Results
Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission.
Conclusion
Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure.
doi:10.1186/1471-2369-7-3
PMCID: PMC1413523  PMID: 16515712

Results 1-9 (9)