Prevalence of anemia and its impact on mortality and hospitalization rate in predialysis patients.

BACKGROUND/AIM: Anemia is associated with increased mortality and morbidity in both early and very late stages of chronic kidney disease (CKD). The aim of this study was to assess whether anemia is a risk factor for mortality or hospitalization in CKD stage 4-5 predialysis patients not yet on dialysis. METHODS: Incident predialysis patients were included between 1999 and 2001 and followed until January 2008 or death. Anemia was defined as mean hemoglobin (Hb) < or =11 g/dl in the 3 months before the start of predialysis. Associations were assessed by Cox regression, linear and logistic regression analysis. RESULTS: A total of 472 patients were included (median follow-up time 12 months, 11% died, 79% started dialysis). Mean Hb was 11.2 g/dl (minimum 7.6, maximum 16.9). Forty-eight percent of patients had anemia at the start of predialysis care. The adjusted mortality risk (hazard ratio, 95% confidence interval) for anemic compared to nonanemic patients was 1.92 (1.04, 3.52). Anemia tended to be related to all-cause but not to non-dialysis-related hospitalization risk. CONCLUSION: At the start of predialysis care, 48% of patients had anemia. Anemia as defined in guideline targets is not associated with an increase in hospitalizations not related to renal replacement therapy, but is likely an important risk factor for mortality in predialysis patients.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Implementation of a vascular access quality programme improves vascular access care.

INTRODUCTION: In the Netherlands an access quality improvement plan (QIP) was introduced by vascular access coordinators (VAC) with the aim to decrease vascular access-related complications by preemptive intervention of malfunctioning accesses. A vascular access QIP was established in 24 centres (46% of all Dutch facilities) and a structural multidisciplinary vascular access meeting was instituted. In these centres, including 2300 patients, a protocol for enhancement of fistula creation and access surveillance programme was implemented, with instruction of physicians and nurses, and rounds to discuss complications and evaluate vascular access interventions. The number and type of vascular access, permanent catheters, thrombosis rates and number of interventions were evaluated at the start and end of the study period. RESULTS: After the surveillance programme, the number of autogenous arterio-venous fistulas (AVFs) had increased significantly from 69 to 77% (P < 0.01), while the use of temporary subclavian vein catheters declined (34% vs 11%) (P < 0.01), with a substantially higher percentage of jugular vein catheters (from 23 to 35%). Interventional treatment of malfunctioning accesses by percutaneous transluminal angioplasty (PTA) (from 0.39 to 0.50 patient/year; P < 0.001)) and surgical revisions (from 0.06 to 0.12 per patient/year; P < 0.001) also increased. CONCLUSION: These data demonstrate that a vascular access QIP resulted in placement of more autogenous AVFs, increased number of PTAs and surgical interventions. These findings suggest that a vascular access care QIP is worthwhile to improve dialysis patients' care and access morbidity.

Determinants of failure of brachiocephalic elbow fistulas for haemodialysis.

OBJECTIVES: The aim of this study was to analyse the results of brachiocephalic fistulas for haemodialysis and to determine possible predictors of failure. PATIENTS AND METHODS: Between April 1999 and September 2004, a consecutive series of 100 autologous brachiocephalic fistulas were created in 96 patients. There were 57 men and 39 women with a mean (SD) age of 59.2 (15.6) years. Data were prospectively gathered. RESULTS: The mean (SD) follow-up was 20.1 (16.4) months. The primary, primary assisted, and secondary patency rates after 6 months were 73.4, 83.2 and 86.4%, respectively. After 1 year, these figures were 54.7, 72.3 and 79.2%, and after 2 years 40.4, 59.2 and 67.5%, respectively. Predictors of failure with regard to primary patency, determined with Cox regression multivariate analysis, included diabetes mellitus (HR 2.81, p < 0.001) and a history of contralateral PTFE loop graft (HR 7.79, p = 0.007). CONCLUSION: Primary patency of brachiocephalic fistulas is comparable to that of radiocephalic fistulas. Primary assisted and secondary patency rates can, however, be brought to a much higher level, especially in patients without diabetes and a large-diameter venous outflow tract.

Anthropometry-based equations overestimate the urea distribution volume in hemodialysis patients.

BACKGROUND: Protein intake in hemodialysis patients can be estimated indirectly from the protein equivalent of total nitrogen appearance (PNA) during the interdialytic period. A reliable estimate of the patient's urea distribution volume (UDV) is required to assess protein intake from PNA values. UDV values are derived frequently from simple anthropometric equations. METHODS: UDV values based on anthropometric methods were compared with UDV values determined by direct dialysate quantitation (DDQ) in 54 stable chronic hemodialysis patients. The anthropometric methods included the following: the Watson equations (WAT), a fixed proportion of postdialysis body weight, 58% for males and 55% for females (% body wt), and skinfold thickness measurements (SFT). Postdialysis blood samples were drawn at 15-minutes postdialysis. RESULTS: UDV(WAT) and UDV(SFT) overestimated UDV(DDQ) by about 8 L [limits of agreement (LOA): 2.6 to 14.2 L] in males and about 6 L (LOA: -0.8 to 12.4 L) in females. The overestimation by UDV(%BW) was even larger: 10.5 L (LOA: 2.0 to 19.0 L) in males and 11.1 L (LOA: 2.1 to 20.1 L) in females. The difference between UDV(%BW) and UDV(DDQ) correlated with the percentage of body fat (r = 0.57) and body mass index (r = 0.48). In a subgroup of seven patients, UDV was also determined by dilution (DIL) of the stable isotope [(13)C]urea. UDV(WAT) and UDV(%BW) overestimated UDV(DIL) significantly. In contrast, UDV(DDQ) was significantly smaller than UDV(DIL), even after correction for incomplete postdialysis equilibration. PNA values calculated using the various UDV estimates were compared with dietary protein intake (DPI) assessed from food records. PNA(DDQ) (61 +/- 10 g/day) did not differ significantly from DPI (63 +/- 13 g/day), but the agreement in individual patients varied considerably (LOA, -24 to 20 g/day). Anthropometric-based PNA values overestimated DPI by 8 to 16 g/day. CONCLUSIONS: Anthropometry-based equations overestimate UDV values in hemodialysis patients, leading to an overestimation of PNA values. Although PNA measurements by DDQ appear to be more reliable for assessing protein intake, PNA(DDQ) values should be interpreted with caution in individual hemodialysis patients.

Relating protein intake to nutritional status in haemodialysis patients: how to normalize the protein equivalent of total nitrogen appearance (PNA)?

BACKGROUND: The protein equivalent of total nitrogen appearance (PNA) is assumed to be a reliable estimate of dietary protein intake in haemodialysis patients. Protein requirements are related to body size. In order to standardize PNA to individual differences in body size, PNA is normalized to various terms related to the patient's body weight. It is not clear which is the most appropriate method to normalize PNA. METHODS: We calculated five commonly used variants of normalized PNA and related them to indices of nutritional status in 57 stable chronic haemodialysis patients, 57 +/- 15 (mean +/- SD) years of age. PNA, determined by direct dialysate quantification, was normalized to actual post-dialysis dry body weight (DBW), normal body weight (DBWnormal), lean body mass (LBM), normal lean body mass (LBMnormal), and 'normalized' body weight (N). Nutritional status was assessed using an index of nutrition composed of anthropometry derived parameters and plasma albumin concentration. RESULTS: PNA(DBW) (0.85 +/- 0.14 g/kg/d) tended to be higher than PNA(DBWnormal) (0.81 +/- 0.14 g/kg/d). PNA(LBM) (1.17 +/- 0.19 g/kg/d) did not differ from PNA(LBMnormal) (1.19 +/- 0.21 g/kg/d). PNA(N) (1.06 +/- 0.14 g/kg/d) was significantly higher than PNA(DBW) and PNA(DBWnormal), but lower than PNA(LBM) and PNA(LBMnormal). Actual PNA (61 +/- 13 g/d) correlated significantly with DBW (r=0.52) and LBM (r=0.63) indicating that large patients eat more protein. Interestingly, actual PNA correlated with plasma albumin (r=0.33) and with the overall index of nutrition (r=0.27) as well. PNA(DBW) correlated negatively with relative DBW (r=-0.32), expressed as a percentage of normal values, indicating that PNA(DBW) is relatively high in underweight patients. In contrast, PNA(DBWnormal) correlated positively with all nutritional parameters as well as with the overall index of nutrition (r=0.33). PNAN and PNA(LBM) did not correlate with the nutritional status, but PNA(LBMnormal) correlated positively with relative DBW (r=0.50) and with overall nutritional status (r=0.34). PNA(DBWnormal) and PNA(LBMnormal) in well-nourished patients showed overlap with the values in patients with evident malnutrition, despite the positive correlation of the normalized PNA values with nutritional status. CONCLUSIONS: Normalizing PNA by DBWnormal and LBMnormal appeared to be the most appropriate method to standardize protein intake in haemodialysis patients. Since actual PNA is the purest estimate of protein intake that correlated with nutritional status, we recommend to evaluate actual PNA as well in studies that relate protein intake to patient outcome.

Assessing dialysis adequacy and dietary intake in the individual hemodialysis patient.

BACKGROUND: Urea kinetic modeling (UKM) and food records are widely used to assess the dialysis adequacy. Clinicians use these methods in individual patients to decide whether the dialysis prescription should be adjusted. We determined the variation in UKM parameters and dietary intake within individual patients in order to determine the required number of UKM measurements, and the number of food recording days to assess dialysis adequacy and dietary intake reliably. METHODS: Session-to-session variation in urea reduction ratio (URR), Kt/V, urea distribution volume (UDVDDQ), and protein catabolic rate (PCR) was determined during three mid-week dialysis sessions in 50 stable hemodialysis patients on three-times per week hemodialysis with a Kt/V of 0.98 +/- 0.13 (mean +/- SD). The dialysis prescription was kept constant. The day-to-day variation in dietary protein intake (DPI) and dietary energy intake (DEI) was determined from seven-day food records. The 90th percentile value of the coefficient of variation (CV) was used to determine the number of measurements. RESULTS: The variation in URR [CV, 2.4% (0.3 to 9.5) median (range)] and in Kt/V [CV, 4.0% (0.6 to 11.6)] was small in the majority of the patients. The variation in UDVDDQ [CV, 4.9% (0.3 to 25.7)] and PCR [CV, 9.3% (0.8 to 28.5)] was considerably larger. The variation in DPI [CV, 17.3% (8.4 to 64.0)] was larger than that in DEI [CV, 12.9% (5.0 to 33.0)]. To assess the URR within +/- 10% of its true value, the average of two measurements was required. Reliable assessment of Kt/V required three measurements. URR and Kt/V could be assessed reliably from a single measurement in 86 and 66% of the patients, but we were not able to distinguish these patients beforehand. Reliable estimation of UDVDDQ required six measurements. The required number of measurements for PCR, DPI, and DEI was determined using a precision of +/- 20%. To assess PCR reliably, three measurements were needed. Estimation of DPI and DEI required seven and five food recording days, respectively. CONCLUSIONS: The session-to-session variation in URR and Kt/V is small in stable hemodialysis patients. Nevertheless, the averaged value of two to three measurements is required to assess the dose of dialysis reliably. Assessment of dietary intake requires at least three PCR measurements or food records for at least one week. Basing clinical decisions on a single dialysis adequacy assessment is an unjustified practice that should be abandoned.

Erythrocyte Na+/Li+ countertransport and Na+/K+-2Cl- co-transport measurement in essential hypertension: useful diagnostic tools or failure? A meta-analysis of 17 years of literature.

1.A meta-analysis of 17 years of literature on erythrocyte Na+/Li+ countertransport (NLCT) and Na+/K+ co-transport (COT) measurements in relation to essential hypertension is presented. The analysis aimed to answer two questions: (i) Which clinical or laboratory variables influence NLCT and COT flux values? (ii) How useful are NLCT and COT measurements as a diagnostic aid in essential hypertension?2. Regression analysis was performed on the mean flux values and relevant clinical and laboratory values. Studies in both normotensive and hypertensive subjects were stratified for variables which showed a significant association with the measured flux. For hypertensive subjects the studies were also stratified for medication. Means of strata were calculated after weighing the mean of a study by the inverse of its own variance and were compared in normotensive as well as hypertensive subjects using a t-test.3.The analysis did not demonstrate systematic effects of laboratory variables for either NLCT or COT. It was found that essential hypertension, family history of hypertension, gender and antihypertensive medication are main determinants for the flux values of both transport systems. After stratification for these determinants, significant differences in weighed mean flux values between normotensive and hypertensive subjects were demonstrated. However, these differences are much smaller than the variance in the weighed mean flux values, suggesting the existence of other unknown variables that strongly affect the flux rates.4.In conclusion, NLCT and COT measurements cannot be of diagnostic use in essential hypertension.

Determination of urea kinetics by isotope dilution with [13C]urea and gas chromatography-isotope ratio mass spectrometry (GC-IRMS) analysis.

1. Stable urea isotopes can be used to study urea kinetics in humans. The use of stable urea isotopes for studying urea kinetic parameters in humans on a large scale is hampered by the high costs of the labelled material. We devised a urea dilution for measurement of the distribution volume, production rate and clearance of urea in healthy subjects and renal failure patients using the inexpensive single labelled [13C]urea isotope with subsequent analysis by headspace chromatography-isotope ratio MS (GC-IRMS) of the [13C]urea enrichment. 2. The method involves measurement of the molar percentage excess of [13C]urea in plasma samples taken over a 4 h period after an intravenous bolus injection of [13C]urea. During the sample processing procedure, the plasma samples together with calibration samples containing a known molar percentage excess of [13C]urea are acidified with phosphoric acid to remove endogenous CO2, and are subsequently incubated with urease to convert the urea present in the plasma samples into CO2. The 13C enrichment of the generated CO2 is analysed by means of GC-IRMS. This method allows measurement of the molar percentage excess of [13C]urea to an accuracy of 0.02%. 3. Reproducibility studies showed that the sample processing procedure [within-run coefficient of variation (CV) < 2.8% and between-run CV < 8.8%] and the GC-IRMS analysis (within-day CV < 1.3% and between-day CV < 1.3%) could be repeated with good reproducibility. 4. In clinical urea kinetic studies in a healthy subject and in a renal failure patient without residual renal function, reproducible values of the distribution volume, production rate and clearance of urea were determined using minimal amounts of [13C]urea (25-50 mg). 5. Because only low [13C]urea enrichments are needed in this urea dilution method using GC-IRMS analysis, the costs of urea kinetic studies are reduced considerably, especially in patients with renal failure.

[Dialysis an the elderly]. / Dialyse bij ouderen.

In the Netherlands, only one third of the patients of 65 years or older with terminal renal failure are currently admitted to dialysis treatment. Dialysis in older patients frequently leads to adequate survival and good subjective quality of life. In other words, age as such is not a contraindication to dialysis. Haemodialysis and peritoneal dialysis have about the same clinical results in older patients, as is the case in younger age groups; the choice depends on patient-linked factors and on the patient's preference. It is to be expected that in a number of years the majority of dialysis patients will be aged 65 years or older.

Renal 131I-hippurate clearance overestimates true renal blood flow in the instrumented conscious dog.

We evaluated renal 131I-hippurate clearance (ERPFhip) as a measure of renal blood flow (RBF) in chronically instrumented conscious dogs. When adjusted for renal hippurate extraction (Ehip, 0.77 +/- 0.01) and hematocrit (Hct, 39.7 +/- 1%), calculated RBFhip (656 +/- 37 ml/min) markedly exceeded renal blood flow measured with renal artery blood flow probes (RBFprobe, 433 +/- 27 ml/min). The discrepancy could not be explained by flow probe calibration, because in vivo comparison of flow probe values with renal venous outflow showed only a slight underestimation of renal blood flow (slope 0.93, 95% confidence interval 0.89-0.97). Redistribution of hippurate from erythrocytes into renal venous plasma during or shortly after blood sampling led to an underestimation of Ehip by 4 +/- 1% and thus could only explain a small part of the difference. Extrarenal hippurate clearance was excluded, because the amount of 131I-hippurate cleared from plasma equaled that appearing in the urine (303 +/- 17 and 307 +/- 17 ml/min). Applying these corrections, we found that RBFhip still exceeded RBFprobe by 37 +/- 3%. These data indicate that renal blood flow measured by the hippurate clearance technique markedly overestimates true renal blood flow. Because other errors were excluded, a combination of sampling of nonrenal blood and intrarenal hippurate extraction from erythrocytes might play a role.

Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension.

UNLABELLED: We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney. METHODS: Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and catheters in the aorta, atrium and both renal veins. RESULTS: Enalaprilat (10 mg intravenously) in conscious dogs with renal artery stenoses produced changes in all stenotic (n = 11) but not in nonstenotic kidney 123I-hippurate renograms (n = 6). Renographic changes correlated significantly with initiation of intrarenal 131I-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of 131I-hippurate and 125I-iothalamate (r = 0.68, r = 0.62, r = 0.84, r = 0.83, respectively) but not with renal blood flow changes (r = 0.34). Furthermore, renal uptake of 131I-hippurate and 125I-iothalamate decreased in stenotic kidneys with a grade II renogram (-52 +/- 11% and -79 +/- 6%, respectively). Iodine-125-hippurate autoradiograms of stenotic kidneys during ACE inhibition showed tracer retention mainly in the proximal tubular cells. Results during osmotic diuresis supported our findings. CONCLUSION: Angiotensin-converting enzyme inhibition-induced hippurate retention curves of poststenotic kidneys appear to result from a sequence of events. A decrease in MAP combined with efferent vasodilation leads to a decrease in intraglomerular capillary pressure. This decrease in pressure causes a decrease in glomerular filtration rate and proximal tubular urine flow. This decrease in turn hampers tubular hippurate transit and transport across the luminal membrane, leading to intrarenal hippurate retention and, in more severe cases, decreased renal hippurate uptake.

Drug-induced changes in renal hippurate clearance as a measure of renal blood flow.

We studied the accuracy of the plasma 131I-hippurate clearance technique to monitor drug-induced changes in renal blood flow (RBF) by comparing it to a flow probe technique in six conscious, chronically instrumented dogs. Placebo caused no change in RBF, either established by hippurate clearance (ERPFhip) or by renal blood flow probe (RBFprobe). Enalaprilate induced a rise in ERPFhip and RBFprobe (+26 +/- 5 and 44 +/- 12%), as did dopamine (+16 +/- 4 and +33 +/- 5%). Intravenous infusion of norepinephrine induced a rise in ERPFhip (+2 +/- 6%, NS) and in RBFprobe (+18 +/- 3%), as did nitroprusside (+14 +/- 4% and +13 +/- 6%, NS). Indomethacin induced a fall in ERPFhip (-8 +/- 2%) and in RBFprobe (-7 +/- 3%, NS), as did angiotensin II (-19 +/- 1 and -26 +/- 3%). Renal hippurate extraction (Ehip) was affected by enalaprilate, dopamine, and angiotensin II (-5 +/- 2, -7 +/- 1, and +5 +/- 2%, respectively). Hematocrit (Hct) was affected by dopamine, norepinephrine, and nitroprusside (+2 +/- 1, +6 +/- 1, and -6 +/- 2%, respectively). Drug-induced changes in ERPFhip correlated well with changes in RBFprobe (r = 0.902, P < 0.01). Changes in Ehip did not independently affect this relation, whereas changes in Hct did: delta RBF(% of baseline) = 1.529 x delta ERPFhip(% of baseline) + 1.296 x delta Hct(% of baseline). These data indicate that drug-induced changes in plasma hippurate clearance can, even when changes in renal hippurate extraction are unknown, be used as a reliable indicator of changes in renal blood flow if changes in hematocrit are taken into account.

Relationship between blood pressure during haemodialysis and ambulatory blood pressure in between dialyses.

BACKGROUND: Ambulatory blood pressure measurements in haemodialysis patients are relevant in view of the high cardiovascular morbidity and mortality in chronic haemodialysis patients. METHODS: Twelve normotensive patients were studied from the beginning of one dialysis until the end of the next (mean 64 h, SD 19 h) using a Spacelabs oscillometric blood-pressure recorder. RESULTS: A circadian blood pressure rhythm was present in six of the 12 patients. In seven patients the lowest pressure recorded (including the dialysis sessions) occurred 5-6 h after dialysis (late post-dialysis dip). Blood pressure did not increase sharply in the hours before dialysis although it increased slightly in the interdialytic interval as a whole, at a mean rate of 5.6 mmHg per 24 h (SD 4.1, P < 0.001). We could not find a blood pressure measurement during dialysis (or combination of measurements) which reliably reflects interdialytic blood pressure: the 95% confidence intervals were 25 mmHg or higher. CONCLUSION: Ambulatory blood pressure measurements are needed for adequate monitoring of the control of blood pressure in haemodialysis patients.

Determination of protein catabolic rate in patients on chronic intermittent hemodialysis: urea output measurements compared with dietary protein intake and with calculation of urea generation rate.

We assessed the agreement between different methods of determining protein catabolic rate (PCR) in hemodialysis patients and the possible influence of postdialysis urea rebound and the length of the interdialytic interval on the PCR determination. Protein catabolic rate derived from measured total urea output was compared with recorded daily protein intake (DPI) and calculated urea generation rate (G), calculated by the interdialytic increase in serum urea and an estimated urea distribution volume using either the Watson equation or 58% of postdialysis body weight, and by single-pool urea kinetic modelling. In 16 patients PCR derived from calculated G by fixed urea distribution volume showed a significant decrease with blood samples obtained 10 minutes after dialysis onward as compared with immediately after dialysis, leading to an approximately 6% decrease at 60 minutes. Protein catabolic rate values derived from blood samples taken 15 to 60 minutes after dialysis were not significantly different. Urea kinetic modelling led to a significant increase in calculated PCR with samples from 5 minutes after dialysis onward and a total increase by 11.5% at 60 minutes. Different methods for determining PCR were compared in 13 clinically stable outpatients treated with conventional hemodialysis on cellulose acetate membrane dialyzers during 1 week. The mean PCR calculated from measured total urea output was 61.3 g/24 hr (range, 43.7 to 83.2 g/24 hr). Assessment of DPI as compared with PCR calculated from measured total urea output was lower by 7.5% (95% confidence intervale [CI], 1.4 to 17.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chronic ACE inhibition on the diagnostic value of renography for renovascular hypertension: a preliminary report.

We compared the effects of acute and chronic ACE inhibition (ACEi) on the 123I-hippurate in the stenotic kidney of two 2-kidney, 1-clip hypertensive dogs. In the period after clip implantation poststenotic renograms without ACEi of both dogs were normal. Acute ACEi always resulted in delayed hippurate handling. Chronic ACEi, however, induced abnormal poststenotic renograms in only 36% of the cases. Withdrawal of chronic ACEi restored the phenomenon of acute ACE-induced delayed hippurate handling within 5 months in both dogs. These data indicate that chronic ACEi or recent ACEi medication reduces the effectiveness of ACEi renography in diagnosing hypertension due to a moderate renal-artery stenosis. This phenomenon may explain why the sensitivity of ACEi renography in human studies varies more than in animal studies.