Nynke Halbesma

Haemodialysis catheters increase mortality as compared to arteriovenous accesses especially in elderly patients

BACKGROUND Catheter use has been associated with an increased mortality risk in haemodialysis patients. However, differences in the all-cause and cause-specific mortality risk between catheter use and arteriovenous access use in young and elderly haemodialysis patients have not yet been investigated. METHODS In this prospective cohort study of 1109 incident haemodialysis patients from 38 centres in the Netherlands, hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated for 2-year all-cause, infection-related and cardiovascular mortality in patients with a catheter as compared to patients with an arteriovenous access stratified for age (< 65 years and ≥ 65 years). RESULTS Of the 1109 patients, 919 had an arteriovenous access and 190 had a catheter. The mortality rate was 76 per 1000 person-years in young patients with an arteriovenous access, 129 per 1000 person-years in young patients with a catheter, 222 per 1000 person-years in elderly patients with an arteriovenous access and 427 per 1000 person-years in elderly patients with a catheter. The adjusted HR was 3.15 (95% CI: 2.09-4.75) for elderly patients with a catheter as compared to young patients with an arteriovenous access. The adjusted HRs in elderly patients with a catheter as compared to elderly patients with an arteriovenous access were 1.54 (95% CI: 1.13-2.12) for all-cause mortality, 1.60 (95%: CI 0.62-4.19) for infection-related mortality and 1.67 (95% CI: 1.04-2.68) for cardiovascular mortality. CONCLUSIONS Especially, elderly haemodialysis patients with a catheter have an increased all-cause, infection-related and cardiovascular mortality risk as compared to patients with an arteriovenous access.

Obesity and mortality risk among younger dialysis patients

BACKGROUND AND OBJECTIVES Many studies show that obesity in dialysis patients is not strongly associated with mortality but not whether this modest association is constant over age. This study investigated the extent to which the relation of body mass index (BMI) and mortality differs between younger and older dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Adult dialysis patients were prospectively followed from their first dialysis treatment for 7 years or until death or transplantation. Patients were stratified by age (<65 or ≥65 years) and baseline BMI (<20, 20-24 [reference], 25-29, and ≥30 kg/m(2)). RESULTS The study sample included 984 patients younger than 65 years and 765 patients 65 years or older; cumulative survival proportions at end of follow-up were 50% and 16%. Age-standardized mortality rate was 1.7 times higher in obese younger patients than those with normal BMI, corresponding to an excess rate of 5.2 deaths/100 patient-years. Mortality rates were almost equal between obese older patients and those with normal BMI. Excess rates of younger and older patients with low compared with normal BMI were 8.7 and 1.1 deaths/100 patient-years. After adjustment for age, sex, smoking, comorbidity, and treatment modality, hazard ratios by increasing BMI were 2.00, 1, 0.95, and 1.57 for younger patients and 1.07, 1, 0.88, and 0.91 for older patients, implying that obesity is a 1.7-fold (95% confidence interval, 1.1- to 2.9-fold) stronger risk factor in younger than older patients. CONCLUSIONS In contrast to older dialysis patients, younger patients with low or very high BMI had a substantially elevated risk for death.

Peritoneal Albumin and Protein Losses Do Not Predict Outcome in Peritoneal Dialysis Patients

BACKGROUND AND OBJECTIVES Peritoneal clearance of albumin-unlike the transport of small molecules-is defined by both vascular surface area and size-selective permeability. Few studies have supported a positive correlation between peritoneal albumin loss and mortality. The aim of this study was to investigate whether baseline peritoneal loss and clearance of albumin and other proteins is a risk factor of death in peritoneal dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All incident peritoneal dialysis patients in our center during the last 15 years were included. Mass-transfer area coefficient of creatinine and peritoneal clearances of albumin, β₂-microglobulin, α₂-macroglobulin, and immunoglobulin G were calculated during a standard peritoneal permeability analysis. The total amount of albumin loss in the dialysate was also calculated. Overall mortality was studied with an intention-to-treat analysis. RESULTS Two hundred fifty-seven patients were included. High baseline albumin clearance was associated with fast transport status, the presence of peripheral arterial disease, and a high comorbidity index, whereas C-reactive protein levels did not differ from the patients with low albumin clearance. Age, high comorbidity score, C-reactive protein levels >10 mg/L, and a low serum albumin were associated with mortality. Peritoneal albumin clearances and albumin loss were not associated with death in crude and adjusted analysis. Similarly, peritoneal clearances of immunoglobulin G, α₂-macroglobulin, and β₂-microglobulin were not determinants of survival. CONCLUSIONS Baseline peritoneal albumin and protein clearances are associated with signs of comorbidity, but this does not have a measurable effect on patient survival.

End stage renal disease and survival in people with diabetes: a national database linkage study

Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. Results: Point prevalence of chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM. Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.

Differences in Progression to ESRD between Black and White Patients Receiving Predialysis Care in a Universal Health Care System

BACKGROUND AND OBJECTIVES Studies performed in the United States showed that blacks progress from CKD to ESRD faster than do whites. Possible explanations are differences in health care system factors. This study investigated whether progression is also faster in a universal health care system, where all patients receive comparable care. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from the PREdialysis PAtient REcord study, a multicenter follow-up study of patients with CKD who started predialysis care in The Netherlands (1999-2011), were analyzed. Time-dependent Cox proportional hazards models were used to estimate the hazard ratio (HR) for starting renal replacement therapy (RRT), and linear mixed models were used to compare renal function decline (RFD) between blacks and whites. To explore possible mechanisms, analyses were adjusted for patient characteristics. RESULTS At initiation of predialysis care, blacks (n=49) were younger and had more diabetes mellitus, higher proteinuria levels, and a higher estimated GFR than whites (n=946). Median follow-up time in months was similar (blacks: 13.9 [boundaries of interquartile range (IQR), 5.3 to 19.5]; whites: 13.1 [IQR, 5.1 to 24.0]). For blacks compared with whites, the crude HR for starting RRT within the first 15 months was 0.86 (95% confidence interval [CI], 0.55 to 1.34) and from 15 months onward, 1.93 (95% CI, 1.02 to 3.68), which increased after adjustment. RFD was faster by 0.18 (95% CI, 0.05 to 0.32) ml/min per 1.73 m(2) per month in blacks compared with whites. CONCLUSION Blacks receiving predialysis care in a universal health care system have faster disease progression than whites, suggesting that health care system factors have a less influential role than had been thought in explaining black-white differences.

Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study.

BackgroundTo investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care.MethodsIn the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT.ResultsA total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07) and 0.05 (0.00;0.11) ml/min/1.73 m2/month respectively) and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14) and 1.16 (1.05;1.28) respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function (adjusted additional decline 0.31 (0.08;0.53) ml/min/1.73 m2/month) and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44)), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target (adjusted additional decline 0.31 (0.04;0.58) ml/min/1.73 m2/month and adjusted HR 2.24 (1.26;3.97)). Therefore, it seems that especially having SBP above the target is harmful.ConclusionsIn pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP) above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT.

Socioeconomic status, comorbidity and mortality in patients with type 2 diabetes mellitus in Scotland 2004–2011: a cohort study

Background Mortality in people with and without diabetes often exhibits marked social patterning, risk of death being greater in deprived groups. This may reflect deprivation-related differences in comorbid disease (conditions additional to diabetes itself). This study sought to determine whether the social patterning of mortality in a population with type 2 diabetes mellitus (T2DM) is explained by differential comorbidity. Methods Hospital records for 70 197 men and 56 451 women diagnosed with T2DM at 25 years of age and above in Scotland during the period 2004–2011 were used to construct comorbidity histories. Sex-specific logistic models were fitted to predict mortality at 1 year after diagnosis with T2DM, predicted initially by age and socioeconomic status (SES) then extended to incorporate in turn 5 representations of comorbidity (including the Charlson Index). The capacity of comorbidity to explain social mortality gradients was assessed by observing the change in regression coefficients for SES following the addition of comorbidity. Results After adjustment for age and Charlson Index, the OR for the contrast between the least deprived and most deprived quintiles of SES for men was 0.79 (95% CI 0.67 to 0.94). For women, the OR was 0.81 (0.67 to 0.97). Similar results were obtained for the 4 other comorbidity measures used. Conclusions The social patterning of mortality in people with T2DM is not fully explained by differing levels of comorbid disease additional to T2DM itself. Other dimensions of deprivation are implicated in the elevated death rates observed in deprived groups of people with T2DM.

GRACE score predicts heart failure admission following acute coronary syndrome

Background: Congestive heart failure (CHF) is a common and preventable complication of acute coronary syndrome (ACS). Nevertheless, ACS risk scores have not been shown to predict CHF risk. We investigated whether the at-discharge Global Registry of Acute Coronary Events (GRACE) score predicts heart failure admission following ACS. Methods and Results: Five-year mortality and hospitalization data were obtained for patients admitted with ACS from June 1999 to September 2009 to a single centre of the GRACE registry. CHF was defined as any admission assigned WHO International Classification of Diseases 10 diagnostic code I50. The hazard ratio (HR) for CHF according to GRACE score was estimated in Cox models adjusting for age, gender and the presence of CHF on index admission. Among 1,956 patients, CHF was recorded on index admission in 141 patients (7%), and 243 (12%) were admitted with CHF over 3.8 median years of follow-up. Compared to the lowest quintile, patients in the highest GRACE score quintile had more CHF admissions (116 vs 17) and a shorter time to first admission (1.2 vs 2.0 years, HR 9.87, 95% CI 5.93–16.43). Per standard deviation increment in GRACE score, the instantaneous risk was more than two-fold higher (HR 2.28; 95% CI 2.02–2.57), including after adjustment for CHF on index admission, age and gender (HR 2.49; 95% CI 2.06–3.02). The C-statistic for CHF admission at 1-year was 0.74 (95% CI 0.70–0.79). Conclusions: The GRACE score predicts CHF admission, and may therefore be used to target ACS patients at high risk of CHF with clinical monitoring and therapies.

High-Sensitivity Cardiac Troponin and the Risk Stratification of Patients With Renal Impairment Presenting With Suspected Acute Coronary Syndrome

Background: High-sensitivity cardiac troponin testing may improve the risk stratification and diagnosis of myocardial infarction, but concentrations can be challenging to interpret in patients with renal impairment, and the effectiveness of testing in this group is uncertain. Methods: In a prospective multicenter study of consecutive patients with suspected acute coronary syndrome, we evaluated the performance of high-sensitivity cardiac troponin I in those with and without renal impairment (estimated glomerular filtration rate <60mL/min/1.73m2). The negative predictive value and sensitivity of troponin concentrations below the risk stratification threshold (5 ng/L) at presentation were reported for a primary outcome of index type 1 myocardial infarction, or type 1 myocardial infarction or cardiac death at 30 days. The positive predictive value and specificity at the 99th centile diagnostic threshold (16 ng/L in women, 34 ng/L in men) was determined for index type 1 myocardial infarction. Subsequent type 1 myocardial infarction and cardiac death were reported at 1 year. Results: Of 4726 patients identified, 904 (19%) had renal impairment. Troponin concentrations <5 ng/L at presentation identified 17% of patients with renal impairment as low risk for the primary outcome (negative predictive value, 98.4%; 95% confidence interval [CI], 96.0%–99.7%; sensitivity 98.9%; 95%CI, 97.5%–99.9%), in comparison with 56% without renal impairment (P<0.001) with similar performance (negative predictive value, 99.7%; 95% CI, 99.4%–99.9%; sensitivity 98.4%; 95% CI, 97.2%–99.4%). The positive predictive value and specificity at the 99th centile were lower in patients with renal impairment at 50.0% (95% CI, 45.2%–54.8%) and 70.9% (95% CI, 67.5%–74.2%), respectively, in comparison with 62.4% (95% CI, 58.8%–65.9%) and 92.1% (95% CI, 91.2%–93.0%) in those without. At 1 year, patients with troponin concentrations >99th centile and renal impairment were at greater risk of subsequent myocardial infarction or cardiac death than those with normal renal function (24% versus 10%; adjusted hazard ratio, 2.19; 95% CI, 1.54–3.11). Conclusions: In suspected acute coronary syndrome, high-sensitivity cardiac troponin identified fewer patients with renal impairment as low risk and more as high risk, but with lower specificity for type 1 myocardial infarction. Irrespective of diagnosis, patients with renal impairment and elevated cardiac troponin concentrations had a 2-fold greater risk of a major cardiac event than those with normal renal function, and should be considered for further investigation and treatment. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Lipid levels and renal function decline in pre-dialysis patients

Background: Little is known about the effect of low-density lipoprotein (LDL) cholesterol, triglyceride (TG), and high-density lipoprotein (HDL) cholesterol levels on renal function decline in patients receiving specialized pre-dialysis care. Methods: In the prospective PREPARE-2 study, incident patients starting pre-dialysis care were included when referred to one of the 25 participating Dutch specialized pre-dialysis outpatient clinics (2004-2011). Clinical and laboratory data were collected every 6 months. A linear mixed model was used to compare renal function decline between patients with LDL cholesterol, TG, or HDL cholesterol levels above and below the target goals (LDL cholesterol: <2.50 mmol/l, TG: <2.25 mmol/l, and HDL cholesterol: ≥1.00 mmol/l). Additionally the HDL/LDL cholesterol ratio was investigated (≥0.4). Results: In our study population (n = 306), the median age was 69 years and 70% were male. Patients with LDL cholesterol levels above the target of 2.50 mmol/l experienced an accelerated renal function decline compared to patients with levels below the target (crude additional decline: 0.10 ml/min/1.73 m2/month, 95% CI 0.00-0.20; p < 0.05). A similar trend was found for TG levels above the target of 2.25 mmol/l (0.05 ml/min/1.73 m2/month, 95% CI -0.06 to 0.16) and for a HDL/LDL cholesterol ratio below 0.4 (0.06 ml/min/1.73 m2/month, 95% CI -0.05 to 0.18). Adjustment for potential confounders resulted in similar results, and the exclusion of patients who were prescribed lipid-lowering medication (statin, fibrate, or cholesterol absorption inhibitor) resulted in a slightly larger estimated effect. Conclusion: High levels of LDL cholesterol were associated with an accelerated renal function decline, independent of the prescription of lipid-lowering medication.