The nutritional status of patients starting specialized predialysis care.

OBJECTIVE: To examine the prevalence of and risk factors for malnutrition at the start of specialized predialysis care. DESIGN: The present analysis was performed on cross-sectional data collected at inclusion in the study. The study included 25 outpatient clinics delivering specialized predialysis care in the Netherlands. SUBJECTS: Three hundred seventy-six incident patients with advanced chronic kidney disease attending one of the participating outpatient clinics. MAIN OUTCOME MEASURE: Subjective global assessment (SGA) of nutritional status. RESULTS: At the start of specialized predialysis care, 11% of patients suffer from moderate protein-energy wasting as measured by SGA. Independent risk factors are age >75 years (Odds ratio [OR], 3.88 [1.74-8.66]), female gender (OR, 2.95 [1.37-6.32]), and having a body mass index <25 kg/m(2) (OR, 2.56 [1.19-5.49]). Estimated glomerular filtration rate was not significantly associated with SGA (OR, 1.63 [0.76-3.48]). CONCLUSIONS: Eleven percent of patients started on specialized predialysis care suffer from moderate protein-energy wasting; risk factors are age >75 years, female gender, and BMI <25 kg/m(2).

Haemoglobin levels and health-related quality of life in young and elderly patients on specialized predialysis care.

BACKGROUND: In predialysis patients, the optimal treatment choices for controlling haemoglobin (Hb) are unknown, because targeting high Hb levels has negative effects--poorer survival--but possible positive effects as well--better health-related quality of life (HRQOL). Moreover, these effects may be different in specific subgroups (e.g. young versus elderly). METHODS: In the PREPARE-2 follow-up study, incident predialysis patients were included (2004-2011) when referred to 1 of the 25 participating Dutch outpatient clinics. HRQOL was assessed at 6-month intervals with the short form-36 (SF-36) questionnaire [physical/mental summary measure and eight subscales (range 0-100)]. A linear mixed model was used to associate Hb [<11, ≥ 11 to <12 (reference), ≥ 12 to <13 and ≥ 13 g/dL] with HRQOL, stratified by prescription of anaemia medication (erythropoietin-stimulating agent (ESA)/iron) and age (young: <65 years and elderly: ≥ 65 years). RESULTS: Only elderly patients (n = 214) not prescribed ESA/iron and with a high Hb (≥ 13 versus ≥ 11 to <12 g/dL) had a statistically significant (P < 0.05) and/or clinically relevant (>3-5 points) higher physical [11.9, 95% confidence interval (CI) 1.7, 22.2] and mental (6.4, 95% CI -1.7, 14.6) summary score. High Hb was not associated with a higher HRQOL in elderly patients who were prescribed ESA/iron. However, only young patients (n = 157) prescribed ESA/iron and with a high Hb (≥ 13 versus ≥ 11 to <12 g/dL) had a higher physical (8.9, 95% CI 2.1, 15.8) and mental (6.2, 95% CI -0.4, 12.8) summary score. CONCLUSIONS: The association of Hb levels with HRQOL differs by age and use of ESA/iron medication on predialysis care. Therefore, medical care should aim for shared decision-making regarding the appropriate Hb target leading to more individualized care.

Is the decline of renal function different before and after the start of dialysis?

BACKGROUND: The presence of glomerular filtration in dialysis patients is associated with improved survival and quality of life. This study explores the time course of the glomerular filtration rate (GFR) between 1 year before and 1 year after the start of haemodialysis (HD) and peritoneal dialysis (PD). METHODS: This study included 1861 incident dialysis patients (NECOSAD cohort; 62% male, 60 ± 15 years, 61% HD, GFR 5.2 ± 3.6 mL/min/1.73 m(2)). A decline of the GFR was estimated using linear mixed-effects models adjusted for age, sex, primary kidney disease, cardiovascular disease and diabetes. The rate of decline was allowed to change at a certain point in time. RESULTS: The decline of the GFR attenuated from -0.53 mL/min/1.73 m(2)/month (95% CI: -0.58, -0.48) in the period before the start of dialysis to -0.12 (95% CI: -0.20, -0.04) at 2-4 months of dialysis in all patients. In HD, decline attenuated from -0.51 (95% CI: -0.57, -0.44) to -0.14 (95% CI: -0.26, -0.02); in PD from -0.55 (95% CI: -0.62, -0.48) to -0.11 (95% CI: -0.23, 0.01). In patients who started dialysis with a GFR equal/above median GFR at dialysis start, the decline attenuated (at 3 months) from -0.70 (95% CI: -0.78; -0.62) to -0.21 (95% CI: -0.36; -0.05). In patients who started dialysis with a GFR below median GFR at dialysis start, the decline attenuated (at 1 month) from -0.73 (95% CI: -0.88; -0.58) to -0.04 (95% CI: -0.27 , 0.19). CONCLUSIONS: The apparent decline of the GFR slows down after 2-4 months of dialysis. This decline was similar in HD and PD patients, although at a different level of GFR. Further studies are needed to examine explanations for this phenomenon.

Pharmacokinetics of dalteparin during haemodialysis.

BACKGROUND/AIMS: Usually, the appropriate dosage of low-molecular-weight heparin during haemodialysis is empirically based on the clinical effect. We studied the pharmacokinetics of dalteparin during standard haemodialysis in different groups of patients to assess the added value of measuring the anti-Xa activity for dose monitoring and adjustments. METHODS: The pharmacokinetics of intravenously administered dalteparin during haemodialysis was studied in 9 patients during 27 haemodialysis sessions. Six patients received a single bolus dose of dalteparin (group 1), and 3 patients received a higher initial bolus dose of dalteparin followed by a second bolus dose after 2 h (group 2). The clinical effect was evaluated by visual inspection for clot formation in the extracorporeal circuit. RESULTS: The pharmacokinetic curve suggests a zero-order process of elimination. The mean decrease in anti-Xa activity (slope) was comparable in all patients. The mean anti-Xa activity at the end of haemodialysis (Clast) was 0.15 IU/ml in group 1 and 0.60 IU/ml in group 2. CONCLUSION: We conclude that measuring anti-Xa activity can be used to monitor the elimination of dalteparin during haemodialysis and is highly reproducible.

Cardiovascular risk estimation in women with a history of hypertensive pregnancy disorders at term: a longitudinal follow-up study.

BACKGROUND: Cardiovascular disease is associated with major morbidity and mortality in women in the Western world. Prediction of an individual cardiovascular disease risk in young women is difficult. It is known that women with hypertensive pregnancy complications have an increased risk for developing cardiovascular disease in later life and pregnancy might be used as a cardiovascular stress test to identify women who are at high risk for cardiovascular disease. In this study we assess the possibility of long term cardiovascular risk prediction in women with a history of hypertensive pregnancy disorders at term. METHODS: In a longitudinal follow-up study, between June 2008 and November 2010, 300 women with a history of hypertensive pregnancy disorders at term (HTP cohort) and 94 women with a history of normotensive pregnancies at term (NTP cohort) were included. From the cardiovascular risk status that was known two years after index pregnancy we calculated individual (extrapolated) 10-and 30-year cardiovascular event risks using four different risk prediction models including the Framingham risk score, the SCORE score and the Reynolds risk score. Continuous data were analyzed using the Student's T test and Mann-Whitney U test and categorical data by the Chi-squared test. A poisson regression analysis was performed to calculate the incidence risk ratios and corresponding 95% confidence intervals for the different cardiovascular risk estimation categories. RESULTS: After a mean follow-up of 2.5 years, HTP women had significantly higher mean (SD) extrapolated 10-year cardiovascular event risks (HTP 7.2% (3.7); NTP 4.4% (1.9) (p<.001, IRR 5.8, 95% CI 1.9 to 19)) and 30-year cardiovascular event risks (HTP 11% (7.6); NTP 7.3% (3.5) (p<.001, IRR 2.7, 95% CI 1.6 to 4.5)) as compared to NTP women calculated by the Framingham risk scores. The SCORE score and the Reynolds risk score showed similar significant results. CONCLUSIONS: Women with a history of gestational hypertension or preeclampsia at term have higher predicted (extrapolated) 10-year and 30-year cardiovascular event risks as compared to women with a history of uncomplicated pregnancies. Further large prospective studies have to evaluate whether hypertensive pregnancy disorders have to be included as an independent variable in cardiovascular risk prediction models for women.

Agreement between different parameters of dialysis dose in achieving treatment targets: results from the NECOSAD study.

BACKGROUND: The recommended parameter of dialysis dose differs between K-DOQI and the European Best Practice Guidelines. It is not well known to what extent an agreement exists between the different parameters, nor if target and delivered dialysis dose are prescribed according to the urea reduction rate (URR), single-pool Kt/V (spKt/V) or equilibrated double-pool Kt/V (eKt/V) and which parameter is most strongly related to mortality. METHODS: In 830 haemodialysis patients from the NECOSAD cohort URR, spKt/V and eKt/V were calculated and compared according to a classification regarding the recommended treatment targets (70%, 1.4 and 1.2, respectively) as well as minimum delivered dialysis dose (65%, 1.2 and 1.05, respectively). Moreover, the relation between treatment dose and survival was assessed using Cox regression analysis. RESULTS: A spKt/V of ≥1.4 and URR ≥70% corresponded with eKt/V ≥1.20 (as reference method) in, respectively, 98.0 and 90.6% of patients. spKt/V of ≥1.2 and URR ≥65% corresponded with eKt/V ≥1.05 in, respectively, 95.5 and 91.2% of patients. Deviations from the reference method were significantly related to differences in urea distribution volume (spKt/V), treatment time (URR) and ultrafiltration volume (URR). The adjusted HR (95% CI) was 0.98 (0.96, 0.99) for URR, 0.51 (0.31, 0.84) for spKt/V and 0.46 (0.30, 0.80) for the eKt/V. CONCLUSION: The use of URR leads to larger disagreement with the reference method (eKt/V) treatment target as compared to spKt/V. Low urea distribution volume, short treatment time and low ultrafiltration volumes are predictive parameters for overestimation of dialysis dose when utilizing the alternative methods spKt/V and URR instead of eKt/V. Delivered eKt/V, spKt/V and URR were all positively related to survival.

Proteinuria as a risk marker for the progression of chronic kidney disease in patients on predialysis care and the role of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment.

BACKGROUND/AIMS: Proteinuria is a risk marker for progression of chronic kidney disease (CKD) and treatment with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) is beneficial in these patients. However, little is known about proteinuria and ACEi/ARB treatment in patients on specialized predialysis care. Therefore, we investigated the association of urinary protein excretion (UPE) and ACEi/ARB treatment with renal function decline (RFD) and/or the start of renal replacement therapy (RRT) in patients on predialysis care. METHODS: In the PREPARE-1 cohort, 547 incident predialysis patients (CKD stages IV-V), referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included (1999-2001) and followed until the start of RRT, mortality, or January 1, 2008. The main outcomes were rate of RFD, estimated as the slope of available eGFR measurements, and the start of RRT. RESULTS: Patients with mild proteinuria (>0.3 to ≤1.0 g/24 h) had an adjusted additional RFD of 0.35 ml/min/1.73 m(2)/month (95% CI: 0.01; 0.68) and a higher rate of starting RRT [adjusted HR: 1.70 (1.05; 2.77)] compared with patients without proteinuria (≤0.3 g/24 h). With every consecutive UPE category (>1.0 to ≤3.0, >3.0 to ≤6.0, and >6.0 g/24 h), RFD accelerated and the start of RRT was earlier. Furthermore, patients starting (n = 16) or continuing (n = 133) treatment with ACEi/ARBs during predialysis care had a lower rate of starting RRT compared with patients not using treatment [n = 152, adjusted HR: 0.56 (0.29; 1.08) and 0.90 (0.68; 1.20), respectively]. CONCLUSION: In patients on predialysis care, we confirmed that proteinuria is a risk marker for the progression of CKD. Furthermore, no evidence was present that the use of ACEi/ARBs is deleterious.

Eye colour and skin pigmentation as significant factors for refractive outcome and residual accommodation in hypermetropic children: a randomized clinical trial using cyclopentolate 1% and tropicamide 1.

PURPOSE: To compare the refractive outcome and residual accommodation with respect to various degrees of iris and skin pigmentation in hypermetropic children using 2 drops of cyclopentolate 1% (C + C) or 1 drop of cyclopentolate 1% and 1 drop of tropicamide 1% (C + T). METHODS: Two hundred fifty-one hypermetropic children were classified according to iris and skin pigmentation (light, medium, dark) and received randomized and double-blind C + C or C + T. Refractive error (spherical equivalent, SEQ) was determined using the Retinomax-K + 3. In 204 subjects, residual accommodation (RA) was determined using the PlusoptiX PowerRefractor. RESULTS: A linear mixed model with a light-irided and light skin-pigmented reference group receiving C + T (mean SEQ +3.10 ± 1.87D) indicated significant less hypermetropia in subjects with a dark iris having a medium- and dark-pigmented skin in C + T, -1.02 ± 0.29 (-1.59/-0.45) and -1.53 ± 0.30 (-2.10/-0.95); and in subjects having a light-, medium- and dark-pigmented skin in C + C, -0.74 ± 0.34 (-1.41/-0.06), -1.26 ± 0.30 (-1.85/-0.66) and -1.84 ± 0.30 (-2.42/-1.26). Similar findings were present for RA. Our model with a light-irided and light skin-pigmented reference group receiving C + T (mean RA +0.84 ± 0.61D) indicated significantly higher RA in dark-irided subjects with medium- and dark-pigmented skin in C + T, +1.05 ± 0.19 (+0.67/+1.43) and +1.35 ± 0.20 (+0.9/+1.74), and in C + C, +1.13 ± 0.21 (+0.71/+1.55) and +1.90 ± 0.19 (+1.51/+2.28). CONCLUSIONS: We found solid evidence that skin pigmentation rather than iris pigmentation is the decisive factor for effectiveness of cycloplegics. Awareness of the limitations of cycloplegic regimens in dark-irided/pigmented children is needed. Our study showed that cyclopentolate 1% combined with tropicamide 1% provides more accurate refractive outcomes both statistically and clinically integrating the factor skin pigmentation for dark-irided subjects.

Wasting and sudden cardiac death in hemodialysis patients: a post hoc analysis of 4D (Die Deutsche Diabetes Dialyse Studie).

BACKGROUND: Wasting is common in hemodialysis patients and often is accompanied by cardiovascular disease and inflammation. The cardiovascular risk profile meaningfully changes with the progression of kidney disease, and little is known about the impact of wasting on specific clinical outcomes. This study examined the effects of wasting on the various components of cardiovascular outcome and deaths caused by infection in hemodialysis patients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,255 hemodialysis patients from 178 centers participating in Die Deutsche Diabetes Dialyse Studie (4D) in 1998-2004. PREDICTOR: Moderate wasting was defined as body mass index, albumin, and creatinine values less than the median (26.7 kg/m(2), 3.8 g/dL, and 6.8 mg/dL, respectively) and C-reactive protein level less than the median (5 mg/L) at baseline. Severe wasting was defined as body mass index, albumin, and creatinine levels less than the median and C-reactive protein level greater than the median at baseline. OUTCOMES & MEASUREMENTS: Risks of sudden cardiac death (SCD), myocardial infarction (MI), stroke, combined cardiovascular events, deaths due to infection, and all-cause mortality were determined using Cox regression analyses during a median of 4 years of follow-up. RESULTS: 196 patients had wasting (severe, n = 109; and moderate, n = 87). Overall, 617 patients died (160 of SCD and 128 of infectious deaths). Furthermore, 469 patients experienced a cardiovascular event, with MI and stroke occurring in 200 and 103 patients, respectively. Compared with patients without wasting (n = 1,059), patients with severe wasting had significantly increased risks of SCD (adjusted HR, 1.8; 95% CI, 1.1-3.1), all-cause mortality (adjusted HR, 1.8; 95% CI, 1.4-2.4), and deaths due to infection (adjusted HR, 2.3; 95% CI, 1.2-4.3). In contrast, MI was not affected. The increased risk of cardiovascular events (adjusted HR, 1.5; 95% CI, 1.0-2.1) was explained mainly by the effect of wasting on SCD. LIMITATIONS: Selective patient cohort. CONCLUSIONS: Wasting was associated strongly with SCD, but not MI, in diabetic hemodialysis patients. Nonatherosclerotic cardiac disease potentially has a major role to account for the increased cardiovascular events in patients with wasting, suggesting the need for novel treatment strategies.

The analysis of competing events like cause-specific mortality--beware of the Kaplan-Meier method.

Kaplan-Meier analysis is a popular method used for analysing time-to-event data. In case of competing event analyses such as that of cardiovascular and non-cardiovascular mortality, however, the Kaplan-Meier method profoundly overestimates the cumulative mortality probabilities for each of the separate causes of death. This article provides an introduction to the problem of competing events in Kaplan-Meier analysis. It explains cumulative incidence competing risk analysis and demonstrates on a cohort of elderly dialysis patients that, in contrast to the Kaplan-Meier method, application of this method yields unbiased estimates of the cumulative probabilities for cause-specific mortality.

Changes in parathyroid hormone, body mass index and the association with mortality in dialysis patients.

BACKGROUND: Obesity is associated with secondary hyperparathyroidism in the general population. It is unknown whether body mass index (BMI) affects parathyroid hormone (PTH) level and its association with mortality in dialysis patients. METHODS: From a prospective cohort study of incident dialysis patients in the Netherlands (NECOSAD), we selected all patients with recorded BMI and PTH at 3 months (baseline) after the start of dialysis [n = 1628, age 59 ± 15 years, BMI 24.7 ± 4.1 kg/m(2), median PTH 13.0 (interquartile range 5.3-29.0) pmol/L]. We assessed associations between BMI and PTH at baseline and between their changes over 3 months by correlation and linear regression analyses. The effect of the changes in PTH on all-cause mortality during a subsequent mean follow-up of 3.2 ± 2 years was assessed by Cox regression analyses. RESULTS: Median PTH levels at baseline were lowest in underweight patients (10.2 pmol/L), followed by normal weight (12.1 pmol/L), overweight (14.0 pmol/L) and obese patients (17.5 pmol/L). The associations were similar in diabetic and non-diabetic patients. A ≥ 5% decrease in BMI (n = 101) over 3 months was accompanied by a 26% decrease in PTH (PTH(ratio) 0.74; P = 0.039), whereas a ≥ 5% increase in BMI (n = 143) was associated with an 11% increase in PTH (PTH(ratio) 1.11; P = 0.026). Compared to patients with stable PTH levels, patients with decreasing PTH in the presence of weight loss showed a 2-fold higher mortality (hazard ratio 2.02, 95% confidence interval 1.45-2.83; P < 0.001), in contrast to those with decreasing PTH in the absence of weight loss. Additional analyses showed that the weight loss was responsible for increased deaths. CONCLUSIONS: PTH is associated with BMI and its longitudinal changes in dialysis patients, both in patients with and without diabetes mellitus. An increased mortality seen for patients with concurrent decreases in PTH and BMI was explained by the weight loss, representing an important confounder for outcome analyses according to levels of PTH. Low and decreasing PTH levels may be symptoms of wasting, which should be taken into account in the care of dialysis patients.

The MDRD formula does not reflect GFR in ESRD patients.

BACKGROUND: The Modification of Diet in Renal Disease (MDRD) equation is widely used for the estimation of glomerular filtration rate (GFR) from plasma creatinine. It has been well validated in patients with various degrees of impaired kidney function, but not in patients with end-stage renal disease (ESRD). Plasma creatinine is determined by GFR and muscle mass. Importance of the latter may increase at low GFR. Our aim was to firstly compare estimated GFR (eGFR by MDRD equation) with measured GFR (mGFR, mean of creatinine and urea clearance) just before the start of dialysis. Secondly, the relationship of eGFR and mGFR with mortality and muscle mass was analysed. METHODS: ESRD patients with 24-h urine collections and a plasma sample available at the start of dialysis [n = 569, 61% male, mean (standard deviation) age 58 (15) years] were selected from the Netherlands Cooperative Study on the Adequacy of Dialysis. Incident dialysis patients were followed until death, transplantation or end of study. RESULTS: mGFR was 6.0 (2.6) and eGFR was 6.8 (2.4) mL/min/1.73 m(2). Although eGFR overestimated mGFR with only 0.8 mL/min/1.73 m(2), limits of agreement ranged from - 4.1 to + 5.6 mL/min/1.73 m(2). The highest eGFR values were associated with the highest mortality rates [adjusted hazard ratio 1.4 (1.0, 1.9)]. eGFR but not mGFR was associated with muscle mass (P = 0.001). CONCLUSIONS: These data imply that estimation of GFR by equations using plasma creatinine in the denominator cannot be used for this purpose in patients with ESRD because the effect of GFR on plasma creatinine is overruled by that of muscle mass.

Association between time of referral and survival in the first year of dialysis in diabetics and the elderly.

OBJECTIVE: The objective of the study was to estimate the association between time of referral and survival during dialysis in diabetics and patients aged≥70 years. DESIGN, SETTING AND SUBJECTS: This study was a prospective follow-up study in 1438 incident dialysis patients (1996-2004, 62% male, 60±15 years) in The Netherlands. Main outcome measures. Referral (time between first pre-dialysis visit to a nephrologist and dialysis initiation) was classified as: late (<3 months), early (3-12 months) or very early (≥12 months). All-cause mortality risk within the first year of dialysis was calculated [HR (95% confidence interval, CI), adjusted for age, sex and primary kidney disease (PKD)]. Additive interaction between time of referral and diabetes mellitus (adjusted for age and sex) or age (adjusted for sex and PKD) was assessed by synergy index [S (95% CI)]. RESULTS: Thirty-two percent were late referred, 12% early and 56% very early; 21% had diabetes; and 30% were ≥70 years. Early and late referrals were associated with increased mortality compared with very early referral [HRadjearly: 1.5 (1.0, 2.4), late: 1.8 (1.3, 2.5)]. A similar trend was observed in diabetics and non-diabetics. However, no interaction between time of referral and diabetes was present [Slate 0.8 (0.4, 1.9), Searly 1.2 (0.4, 3.6)]. Likewise, in patients aged<70 and ≥70 years, time of referral was associated with increased mortality, without interaction [Slate 0.9 (0.4, 1.8), Searly 0.8 (0.3, 2.0)]. CONCLUSION: Late referral is associated with increased mortality in the first year of dialysis. Diabetes or high age does not have an additional worsening effect, implying that timely referral is important in future dialysis patients irrespective of diabetes or high age.

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.

BACKGROUND: To 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. METHODS: In 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. RESULTS: A 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. CONCLUSIONS: In 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.

Survival in dialysis patients is not different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

BACKGROUND: On dialysis, survival among patients with diabetes mellitus is inferior to survival of non-diabetic patients. We hypothesized that patients with diabetes as primary renal disease have worse survival compared to patients with diabetes as a co-morbid condition and aimed to compare all-cause mortality between these patient groups. METHODS: Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a multicenter, prospective cohort study in which new patients with end stage renal disease (ESRD) were monitored until transplantation or death. Patients with diabetes as primary cause of ESRD were compared with patients with diabetes as co-morbid condition and both of these patient groups were compared to patients without diabetes. Analysis was performed using Kaplan-Meier and Cox regression. RESULTS: Fifteen % of the patients had diabetic nephropathy as primary renal disease (N = 281); 6% had diabetes as co-morbid condition (N = 107) and 79% had no diabetes (N = 1465). During follow-up 42% of patients (N = 787) died. Compared to non-diabetic patients, mortality risk was increased for both patients with diabetes as primary renal disease HR: 1.9 (95% CI 1.6, 2.3) and for patients with diabetes as co-morbid condition HR: 1.7 (95% CI 1.3, 2.2). Mortality was not significantly higher in patients with diabetes as primary renal disease compared to patients with diabetes as co-morbid condition (HR 1.06; 95% CI 0.79, 1.43). CONCLUSIONS: This study in patients with ESRD showed no survival difference between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition. Both conditions were associated with increased mortality risk compared to non-diabetic patients.

Benefit of kidney transplantation beyond 70 years of age.

BACKGROUND: Kidney transplantation generally improves long-term survival in patients with end-stage renal disease. However, in patients older than 70 years of age, only limited data are available that directly compare the potential survival benefit of transplantation versus dialysis. METHODS: All patients aged above 70 years who started dialysis between 1990 and 2005 and were waitlisted for kidney transplantation were included in the study. They were categorized according to time periods of inclusion (1990-99 vs 2000-05). Survival rates of altogether 286 dialysis patients were analyzed with a Kaplan-Meier model, as well as with a time-dependent Cox model. Comparisons were made between those who received a transplant and those who did not, and further between the two time periods. RESULTS: Median age at inclusion was 73.6 years (interquartile range 72.3-75.6). Two hundred and thirty-three patients (81%) received a kidney transplant during follow-up. Transplant recipients experienced an increased mortality in the first year after transplantation when compared to waitlisted patients. Patients starting dialysis between 1990 and 1999 had no significant long-term benefit of transplantation; HR for death 1.01 (0.58-1.75). In contrast, there was a substantial long-term benefit of transplantation among those starting dialysis after 2000; HR for death 0.40 (0.19-0.83), P = 0.014. CONCLUSIONS: Survival after kidney transplantation in patients over 70 years has improved during the last decade and offers a survival advantage over dialysis treatment. Our experience supports the use of kidney transplantation in this age group if an increased early post-operative risk is accepted. This transplant policy may be challenged for priority reasons.

Observational studies are complementary to randomized controlled trials.

Randomized controlled trials (RCTs) are considered the gold standard study design to investigate the effect of health interventions, including treatment. However, in some situations, it may be unnecessary, inappropriate, impossible, or inadequate to perform an RCT. In these special situations, well-designed observational studies, including cohort and case-control studies, may provide an alternative to doing nothing in order to obtain estimates of treatment effect. It should be noted that such studies should be performed with caution and correctly. The aims of this review are (1) to explain why RCTs are considered the optimal study design to evaluate treatment effects, (2) to describe the situations in which an RCT is not possible and observational studies are an adequate alternative, and (3) to explain when randomization is not needed and can be approximated in observational studies. Examples from the nephrology literature are used for illustration.

Pre-dialysis patients' perceived autonomy, self-esteem and labor participation: associations with illness perceptions and treatment perceptions. A cross-sectional study.

BACKGROUND: Compared to healthy people, patients with chronic kidney disease (CKD) participate less in paid jobs and social activities. The aim of the study was to examine a) the perceived autonomy, self-esteem and labor participation of patients in the pre-dialysis phase, b) pre-dialysis patients' illness perceptions and treatment perceptions, and c) the association of these perceptions with autonomy, self-esteem and labor participation. METHODS: Patients (N = 109) completed questionnaires at home. Data were analysed using bivariate and multivariate analyses. RESULTS: The results showed that the average autonomy levels were not very high, but the average level of self-esteem was rather high, and that drop out of the labor market already occurs during the pre-dialysis phase. Positive illness and treatment beliefs were associated with higher autonomy and self-esteem levels, but not with employment. Multiple regression analyses revealed that illness and treatment perceptions explained a substantial amount of variance in autonomy (17%) and self-esteem (26%). The perception of less treatment disruption was an important predictor. CONCLUSIONS: Patient education on possibilities to combine CKD and its treatment with activities, including paid work, might stimulate positive (realistic) beliefs and prevent or challenge negative beliefs. Interventions focusing on these aspects may assist patients to adjust to CKD, and ultimately prevent unnecessary drop out of the labor market.

CCR5 deletion protects against inflammation-associated mortality in dialysis patients.

The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5 Delta 32) leads to deficiency of the receptor. We hypothesized that CCR5 Delta 32 modulates inflammation-driven mortality in patients with ESRD. We studied the interaction between CCR5 genotype and levels of high-sensitivity C-reactive protein (hsCRP) in 603 incident dialysis patients from the multicenter, prospective NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort. CCR5 genotype and hsCRP levels were both available for 413 patients. During 5 yr of follow-up, 170 patients died; 87 from cardiovascular causes. Compared with the reference group of patients who had the wild-type CCR5 genotype and hsCRP 10 mg/L (n = 108) had an increased risk for mortality (HR: 1.82; 95% CI: 1.29 to 2.58). However, those carrying the deletion allele with hsCRP > 10 mg/L (n = 25) had a mortality rate similar to the reference group; this seemingly protective effect of the CCR5 deletion was even more pronounced for cardiovascular mortality. We replicated these findings in an independent Swedish cohort of 302 ESRD patients. In conclusion, the CCR5 Delta 32 polymorphism attenuates the adverse effects of inflammation on overall and cardiovascular mortality in ESRD.

Screening: why, when, and how.

Screening refers to the early detection of individuals with unrecognized disease or with early stages of disease among a population. Early detection allows early medical intervention, which may ultimately slow progression of the disease and reduce both morbidity and mortality. As such, screening is an important tool in improving public health. In 1968, Wilson and Jungner proposed 10 criteria to consider prior to starting screening for a disease. This review discusses these criteria when applied to screening for chronic kidney disease with additional focus on (1) the validity of the test to be used for screening; (2) which part of the population to screen; and (3) forms of bias to consider in screening.