[show abstract][hide abstract] ABSTRACT: Developing guidelines on a subject as broad as hypertension is difficult, especially when the guidance relates to hypertension in the chronic kidney disease (CKD) population. The Kidney Disease: Improving Global Outcomes Guideline Development Group has applied a rigorous methodology in reviewing all available evidence, and their recommendations are consistent with the evidence-based approach. As a result, the European Renal Best Practice endorses most of its recommendations. However, the Work Group feels that some additional advice could help clinicians in daily practice: (i) individualization of treatment should be taken into account, especially (cardiovascular) co-morbidities, age, gender and race; (ii) side-effects, such as postural dizziness should be monitored closely, particularly in elderly, diabetics and patients with arterial stiffness; (iii) the importance of salt restriction should not be neglected; (iv) although angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blocker (ARBs) remain a cornerstone in the management of hypertension, and especially cardiovascular protection, in some particular situations such as in advanced CKD and in patients without proteinuria, their role is less well defined; (v) as most CKD patients need more than one antihypertensive drug to achieve blood pressure control, the specific (renal) (dis)advantages of other classes than ACE-I or ARB should be taken into account.
[show abstract][hide abstract] ABSTRACT: Hypomagnesemia predicts cardiovascular morbidity and mortality in the general population and accelerated loss of kidney function in renal transplant recipients and diabetics. It is associated with risk factors for cardiovascular and renal injury such as hyperaldosteronism, endothelial dysfunction, oxidative stress, insulin resistance, and hypertension. We aimed to establish the prognostic significance of hypomagnesemia for all-cause mortality and decline in estimated glomerular filtration rate (eGFR) in chronic kidney disease.
Baseline parameters and serial follow-up measurements of serum creatinine were obtained in 1650 patients with chronic kidney disease and follow-up in a tertiary hospital between January 2002 and June 2011. We used Cox proportional hazards regression to assess the predictive value of magnesium for all-cause mortality and a random-effects mixed linear model for longitudinal analysis of the effect of serum magnesium on eGFR decline.
After a median follow-up of 5.1 years, 284 deaths occurred. Higher magnesium was associated with reduced mortality (adjusted hazard ratio 0.930 per 0.1 mg/dL increase; 95% confidence interval [CI], 0.887-0.974; P = .002) after adjustment for potential confounders including age, sex, diabetes, kidney function, and hypertension. Patients with low (<1.8 mg/dL) versus high (>2.2 mg/dL) serum magnesium had a 61% increased mortality risk (adjusted hazard ratio 1.613; 95% CI, 1.113-2.338; P = .012). On average, eGFR changed by 0.934 per year (95% CI, 0.927-0.941; P <.0001) or an annual decrease of 6.6%. After adjustment for age, sex, diabetes, and hypertension, this change was modified by a factor of 1.033 (95% CI, 1.003-1.065; P = .032) per 1-mg/dL increase in baseline magnesium, corresponding to an annual eGFR decrease of 3.5%. The effect of magnesium lost significance after adjustment for additional covariates, including diuretics.
Hypomagnesemia predicts mortality and kidney function decline in chronic kidney disease patients. Confounding factors and treatment effects may affect these associations. Its potential as a modifiable risk factor remains to be established.
The American journal of medicine 07/2013; · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659-0.776) for pulse wave velocity, 0.670 (95% CI 0.604-0.736) for central augmentation pressure, and 0.595 (95% CI 0.529-0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104-1.649; P=0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219-1.814; P<0.001) remained independent predictors of outcome. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in renal transplant recipients. As single parameter of wave reflection, central augmentation pressure was better than central augmentation index. Combined measurement of pulse wave velocity and central augmentation pressure may contribute to an accurate cardiovascular risk estimation in this heterogeneous population.
[show abstract][hide abstract] ABSTRACT: The degree of chronic kidney disease (CKD) is currently expressed in terms of GFR, which can be determined directly or estimated according to different formulas on the basis of serum creatinine and/or cystatin C measurements (estimated GFR [eGFR]). The purpose of this study was to investigate whether eGFR values are representative for uremic toxin concentrations in patients with different degrees of CKD.
Associations between eGFR based on serum cystatin C and different uremic solutes (mol wt range 113 to 240 D; determined by colorimetry, HPLC, or ELISA) were evaluated in 95 CKD patients not on dialysis (CKD stage 2 to 5). The same analysis was also applied for six other eGFR formulas.
There was a substantial disparity in fits among solutes. In linear regression, explained variance of eGFR was extremely low for most solutes, with eGFR > 0.4 only for creatinine. The other eGFR formulations gave comparably disappointing results with regard to their association to uremic solutes. Relative similarity in R(2) values per solute for the different eGFR values and the strong disparity in values between solutes suggest that the differences in R(2) are mainly due to discrepancies in solute handling apart from GFR.
eGFR is poorly associated with concentrations of all studied uremic toxins in patients with different degrees of CKD, correlates differently with each individual solute, and can thus not be considered representative for evaluating the accumulation of solutes in the course of CKD.
Clinical Journal of the American Society of Nephrology 06/2011; 6(6):1266-73. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Radiographic calcification and arterial stiffness each individually are predictive of outcome in dialysis patients. However, it is unknown whether combined assessment of these intermediate endpoints also provides additional predictive value.
Scoring of abdominal aortic calcification (AAC) using plain lateral abdominal x-ray and measurement of carotid-femoral pulse wave velocity (PWV) were performed in a cohort of 1084 prevalent dialysis patients recruited from 47 European dialysis centers.
During a follow-up of 2 years, 234 deaths and 91 nonfatal cardiovascular (CV) events occurred. Compared with the lowest tertile of AAC, the risk of an event was increased by a factor 3.7 in patients with a score of 5 to 15 (middle tertile), and by a factor 8.6 in patients with scores of 16 to 24. Additionally, each 1-m/s increase in PWV was associated with a 15% higher risk. At higher AAC (scores ≥ 5), the effect of PWV was attenuated because of a negative PWV × AAC interaction (hazard ratio [HR]: 0.895 and 0.865 for middle and upper AAC tertiles). After accounting for age, diabetes, and serum albumin, AAC and PWV remained independent predictors of outcome.
AAC and central arterial stiffness are independent predictors of mortality and nonfatal CV events in dialysis patients. The risk associated with an increased PWV is less pronounced at higher levels of calcification. Assessment of AAC and PWV is feasible in a clinical setting and both may be used for an accurate CV risk estimation in this heterogeneous population.
Clinical Journal of the American Society of Nephrology 01/2011; 6(1):153-9. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Arterial stiffness is a strong predictor of outcome. Hypomagnesaemia, by its association with arterial hypertension, endothelial dysfunction, dyslipidaemia and inflammation, might affect vascular stiffness. As hypomagnesaemia is common in renal transplant recipients (RTR), we examined its potential association with arterial stiffness.
Cross-sectional analysis. Evaluation of vascular stiffness in 512 RTR from two university centres at a median of 72 months post-transplantation. Determination of carotid-femoral pulse wave velocity (PWV) (SphygmoCor). A multiple linear regression analysis was used to investigate the independent relationship between magnesium serum level and PWV with the following covariates: age, diabetes, smoking status, body mass index, blood pressure, heart rate (HR), C-reactive protein (CRP), high-density lipoprotein cholesterol, parathyroid hormone and use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, calcium channel blockers, statins and calcineurin inhibitors next to their drug levels.
Lower serum magnesium was independently associated with PWV (P = 0.018) in addition to age, CRP, HR, diabetes and mean arterial pressure (model R(2) = 0.45; P < 0.001). The relationship between magnesium and PWV was attenuated (P = 0.054) after adjustment for the use of sirolimus, which was associated with higher magnesium levels (P<0.001) and lower PWV (P = 0.013). In patients >55 years (median age), however (low), magnesium remained an independent predictor of PWV (P = 0.024) after accounting for the same covariates.
Serum magnesium is an independent predictor of arterial stiffness in RTR, especially in patients >55 years.
[show abstract][hide abstract] ABSTRACT: The Genius is a convenient single-pass batch hemodialysis system. Dialysate is heated during the preparation phase. Once the container is filled at one of the three available starting temperatures, dialysate cools spontaneously. As dialysate temperature plays an important role in hemodynamic stability, knowledge of the instantaneous dialysate temperature is important. We documented the evolution of dialysate temperature during Genius dialysis with dialysate prepared at two different temperatures (low and medium) as well as its effect on blood temperature and hemodynamic stability. Genius dialysis was compared to isothermic dialysis obtained by a module programmed to obtain a constant blood temperature. With Genius, dialysate temperature progressively decreased from 36.3 (low) and 37.6°C (medium) in the beginning to 34.4 and 35.3°C at the end of the session, both following first-order kinetics. During isothermic dialysis, dialysate cooled from 37.3 to 35.4°C, being warmer than with Genius low. Blood temperature decreased during dialysis with Genius low, from 36.4 to 36.2°C, whereas with medium temperature, blood temperature initially rose from 36.4°C at 15 min to 36.5 and 36.6°C at 30 and 60 min, respectively, followed by a decrease from 180 min onward, to 36.4°C at the end. During isothermic dialysis, blood temperature remained stable, as expected. Blood pressure decreased during all three schedules, with the highest value at 15 min during isothermic dialysis, and at the end of the session, the lowest value with isothermic dialysis.
[show abstract][hide abstract] ABSTRACT: Objectives: Noninvasive estimation of central blood pressure (BP) from radial artery pressure waveforms is increasingly applied. We investigated the impact of radial artery waveform calibration on central BP assessment and calculated pressure amplification, with focus on the one-third rule used to estimate mean arterial BP (MAP).
Methods: Pressure waveforms were noninvasively measured at the radial and carotid arteries in 1873 individuals (age 45.8±6.1 years). Radial and carotid artery waveforms were calibrated using brachial artery DBP and SBP, MAP estimated with the one-third rule and MAP estimated as brachial DBP along with 40% of brachial artery pulse pressure.
Results: Central SBP obtained via a transfer function was 123.5 ± 15.7, 117.8 ± 14.2 and 126.0 ± 15.4 mmHg (mean ± SD) following above-mentioned three calibration schemes, respectively. Using the same calibration schemes, carotid artery SBP was 131.4 ± 15.2, 118.4 ± 14.4 and 126.8 ± 15.7 mmHg, respectively. Central-to-brachial amplification was 13.0 ± 3.6 mmHg using second method as compared with 4.6 ± 3.8 mmHg with third method. Brachial-to-radial amplification was actually negative (−6.3 ± 4.5 mmHg) using second method, whereas 3.4 ± 5.5 mmHg was found with third method.
Conclusion: Both carotid artery SBP and central SBP obtained via a transfer function are highly sensitive to the calibration of the respective carotid artery and radial artery pressure waveforms. Our data suggest that the one-third rule to calculate MAP from brachial cuff BP should be avoided, especially when used to calibrate radial artery pressure waveforms for subsequent application of a pressure transfer function. Until more precise estimation methods become available, it is advisable to use 40% of brachial pulse pressure instead of 33% to assess MAP.
Journal of Hypertension 01/2010; 28(2):300–305. · 3.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
Accurate cardiovascular risk estimation in dialysis patients remains challenging because different pathogenetic mechanisms act simultaneously in this heterogeneous population. Radiographic calcification, aortic stiffness and wave reflection, have each individually been proven to be reliable surrogate markers for outcome. We aimed to explore to what extent these parameters intermutually provide complementary or overlapping information.
[show abstract][hide abstract] ABSTRACT: There remains debate about the screening strategies for albuminuria. This study evaluated whether a screening strategy in an apparently healthy population based on basic clinical and biochemical parameters could be more effective than a strategy where screening for albuminuria is performed unselectively.
The Unreferred Renal Insufficiency (URI) Study is a cross-sectional study on the prevalence of metabolic risk factors in Belgian workers, volunteering to be screened during a routine yearly occupational check-up. Subjects (n = 295) with treated hypertension, known diabetes, treated dyslipidaemia, cardiovascular and renal disease were excluded. Among 1,191 apparently healthy subjects, 23% had unknown hypertension, 13% had impaired glucose tolerance, 15.4% had normoalbuminuria, 4.2% had microalbuminuria and 0.4% had macroalbuminuria. Subjects with resting heart rate ≥85 bpm, plasma glucose ≥5.6 mmol/L and blood pressure ≥140/90 mmHg were associated with albuminuria of any degree. A strategy where only subjects with at least one of these risk factors (n = 431) were screened for albuminuria, would identify all subjects with macroalbuminuria (5/5), 64% of those with microalbuminuria (32/50), and less than half of those with normoalbuminuria (81/183). An alternative strategy whereby subjects were first screened for presence of albuminuria, and additional cardiovascular risk factors were only measured in subjects positive for albuminuria (n = 238), would identify only 27% (118/431) of the subjects with additional and potentially modifiable cardiovascular risk factors. On the other hand, half of the subjects in this study with albuminuria (120/238, of which 102 had normoalbuminuria), had no additional cardiovascular risk factor at all.
Screening an apparently healthy population directly for albuminuria will result in a high percentage of false positives, mostly measured in the normal range. Screening for microalbuminuria and macroalbuminuria based on presence of additional, potentially modifiable risk factors appears to be more beneficial. Trial registration 2006 NCT00365911.
PLoS ONE 01/2010; 5(10):e13328. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Susceptibility to infection and thrombosis of intravascular catheters is increased by surface irregularities, which might be prevented by coating.
BaSO4 release from conventional haemodialysis catheters (CC) and modified catheters (MC) which had been coated with a surface-modifying additive (SMA) was assessed in vivo and in vitro. For the in vivo part, patients were randomized to receive a temporary CC or MC, with crossover after 1 week. After retrieval, catheters were examined using scanning electron microscopy to assess surface integrity, and an in vitro model of catheter exposure to the bloodstream was used to evaluate surface morphology and susceptibility to bacterial adhesion and proliferation.
BaSO(4) moieties covered 14.7 +/- 3.7% of the surface of unused CC. After in vivo use in 16 patients, 62.7 +/- 32.9 x 10(3) holes/mm(2) were detected, indicating BaSO(4) detachment from 3.3 +/- 1.7% of the catheter surface. No defects were observed in unused CC and in MC, whether used or unused. After incubation of four catheters (two of each type) with Staphylococcus epidermidis, the two degraded CC showed an immediate and strong bacterial growth as indicated by an increase in medium impedance of 0.512%/10 min compared to -0.021%/10 min in MC (P < 0.001).
Short-term exposure of CC to the bloodstream causes BaSO(4) particle release, resulting in surface irregularities predisposing to bacterial proliferation. BaSO(4) release can be prevented by SMA coating.
[show abstract][hide abstract] ABSTRACT: New-onset diabetes after transplantation (NODAT) is a frequent complication and has an impact on patient and graft survival. Hypomagnesemia is common in both renal transplant recipients and in diabetics. This study examines the relationship between hypomagnesemia, NODAT and the type of immunosuppression in renal transplant recipients. We conducted a retrospective single-center analysis (2002-2008) in order to assess NODAT the first year posttransplantation as defined by American Diabetes Association criteria. Serum magnesium (Mg) levels were defined as the median of all Mg levels registered during the first month posttransplantation. Patients with NODAT (N = 75; 29.5%) versus non-NODAT had lower Mg levels (p < 0.001). Patients with an Mg level < versus > or = 1.9 mg/dL showed a faster development of NODAT (log-rank p < 0.001). Mg levels were lower in patients on calcineurin inhibitors (CNI) versus no CNI patients (p < 0.001). Mg levels, albumin, BMI, triglycerides, posttransplantation hyperglycemia, tacrolimus levels and the use of sirolimus were predictors of NODAT in the multivariate analysis. Hypomagnesemia was an independent predictor of NODAT in renal transplant recipients. We confirm that the use of CNI is associated with NODAT, but, to a large extent, this effect seems attributable to the induction of hypomagnesemia. After adjustment for Mg, sirolimus was also associated with NODAT.
American Journal of Transplantation 08/2009; 9(9):2140-9. · 6.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: The supposed lack of a hemodynamic impact of peritoneal dialysis (PD) has been challenged recently in different studies, although the observed effects are still far below those seen on hemodialysis (HD), and the underlying mechanisms are unclear.
Literature overview based on Pubmed search with key words 'peritoneal dialysis, acute dwell, hemodialysis'.
Hemodynamic effects of an acute PD dwell seem to be consistent, but rather limited. Increasing peritoneal pressure, causing enhanced preload and thus better cardiac output, and vasoactive reactions induced by incompatibility of the dialysis fluid seem to be the most prominent causes. The role of hyperglycemia is a matter of debate. In view of the repetitive character of the insults, especially during APD, more in depth investigation of this phenomenon is warranted.
Contributions to nephrology 02/2009; 163:96-101. · 1.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: Biological purity of dialysis water is considered as one of the primary conditions to deliver optimal haemodialysis.
The present study explores the added value of a novel cytokine (IL-1ss) induction assay, using a monocytic THP-1 cell line, compared to the classical detection methods for microbial dialysis fluid contaminants.
In contrast to the Limulus Amebocyte Lysate (LAL)-test, which only detects intact lipopolysaccharide (LPS), the THP-1 assay was also sensitive to peptidoglycan, short bacterial DNA fragments and LPS fragments <5 kD. The purity of 269 dialysis fluid samples was tested by the THP-1 assay and compared to the LAL-test. Two hundred and sixty samples complied with the definition of 'pure' dialysis fluid as laid down in the European Pharmacopeia (European Best Practice Guidelines for Hemodialysis. Section IV. Dialysis fluid purity. Nephrol Dial Transplant 2002; 17: 45-62) but 27 of these so-called pure dialysates (10.3%) provoked a pro-inflammatory response in the THP-1 assay. Furthermore, among the 230 samples that complied the definition of an ultrapure dialysis fluid, 21 samples (9.1%) were pro-inflammatory. These data illustrate that this novel bio-assay detects microbiological entities with an inflammatory potential that cannot be found by the classical LAL screening method.
Adding this novel THP-1 assay to the classical methods will be helpful in the prevention of biofilm formation in the delivery system and should have relevance by more accurate detection of dialysate contamination, hence decreasing micro-inflammation in the haemodialysis patient.
[show abstract][hide abstract] ABSTRACT: Patients with chronic kidney disease stage 5 have a high prevalence of vascular calcification, but the specific anatomical distribution and severity of abdominal aortic calcification (AAC), in contrast to coronary calcification, is less well documented. AAC may be recorded using plain radiographs. The present report is an analysis of baseline data on AAC in patients enrolled in the CORD (Calcification Outcome in Renal Disease) study.
A total of 47 centres in six European countries participated in this cross-sectional study. Inclusion criteria were age >or=18 years and duration of dialysis >or=3 months. Lateral lumbar radiography of the abdominal aorta was used to determine the overall AAC score, which is related to the severity of calcific deposits at lumbar vertebral segments L1-L4. The reliability of the method was tested by double reading of 64 radiographs (coefficient of correlation 0.9).
A lateral lumbar radiograph was obtained in 933 patients. Calcification (AAC score >or= 1) was present in 81% of the patients; its severity increased significantly from L1 to L4 (P < 0.0001) and affected all of these segments in 51% of patients. Independent predictors for the presence and severity of calcification were age (odds ratio [OR] 1.103/year; P < 0.0001), duration of dialysis (OR 1.110/year; P = 0.002) and history of cardiovascular disease (OR 3.247; P < 0.0001).
AAC detected by lateral lumbar radiograph is associated with several risk factors of uraemic calcification. This semi-quantitative method is more widely available and less expensive than the current procedures for studying calcification and could form part of a pre-transplant workup and cardiovascular risk stratification.